Sang Froid in a time of trouble: is a vaccine against HIV possible?
© Plotkin. 2009
Received: 25 November 2008
Accepted: 02 February 2009
Published: 02 February 2009
Since the announcement of the STEP trial results in the past months, we have heard many sober pronouncements on the possibility of an HIV vaccine. On the other hand, optimistic quotations have been liberally used, from Shakespeare's Henry V 's "Once more unto the breach, dear friends" to Winston Churchill's definition of success as "going from one failure to another with no loss of enthusiasm". I will forgo optimistic quotations for the phrase "Sang Froid", which translates literally from the French as "cold blood"; what it really means is to avoid panic when things look bad, to step back and coolly evaluate the situation. This is not to counsel easy optimism or to fly in face of the facts, but I believe that while the situation is serious, it is not desperate.
I should stipulate at the outset that I am neither an immunologist nor an expert in HIV, but someone who has spent his life in vaccine development. What I will try to do is to provide a point of view from that experience.
There is no doubt that the results of STEP were disappointing: not only did the vaccine fail to control viral load, but may have adversely affected susceptibility to infection. But HIV is not the only vaccine to experience difficulties; what lessons can we glean from prior vaccine development?
Lessons from vaccinology
First, look at an uncomplicated example: the rubella vaccine. This is a live attenuated virus that was isolated in WI-38 fetal fibroblasts during the 1962/63 rubella pandemic and attenuated by low temperature passage in those same cells . By selection of clones replicating at low temperature, we obtained a virus that consistently multiplied in seronegative humans and that evoked both humoral and mucosal immune responses that blocked superinfection . Why was it successful in giving immunity? Of course, the answer is this: neutralizing antibodies to rubella present in the serum and on the mucosa are correlates of protection in preventing both nasopharyngeal implantation and subsequent viremia .
However, things are not always that easy. Take the paramyxoviruses measles and respiratory syncytial virus (RSV) as examples. Live measles virus has been a great success in eliminating the disease, but in the early days there was also a licensed killed measles vaccine. Unfortunately, when vaccinated children were exposed to wild measles they suffered an atypical disease that included severe pulmonary, hepatic and dermatologic manifestations. Similarly, a formalin inactivated RSV vaccine was tested in infants, many of whom developed severe respiratory disease after subsequent natural infection with the virus .
Severe reactions to Inactivated Measles and RSV Vaccines
Following exposure, vaccinees had exaggerated disease in lungs.
Pathology included immune complex deposition and high replication in the lungs.
Vaccines elicited non-protective, low avidity, waning antibodies.
Vaccines elicited strong CD4+ proliferation with a Th2 cytokine response, including IL-13
Caused cessation of use of both vaccines
Another type of misadventure happened with the first licensed rotavirus vaccine. This was an orally administered mixture of a simian rotavirus and reassortants of human and simian rotaviruses in which the simian virus contributed 10 of the 11 double-stranded RNA segments. Although protective, it caused intussusception (intestinal invagination) in approximately one in 10,000 vaccinees . This happened because the supposedly attenuated simian vector retained pathogenicity for the infant intestine, causing diarrhea and fever . This problem was solved in my former laboratory by substituting a bovine rotavirus as vector, and in another lab, by classical attenuation of a human rotavirus [11, 12]. Neither of the new vaccines causes intussusception [13, 14]. The point is that the choice of a supposedly attenuated vector is a key issue, and that the wrong choice of vector brings safety problems.
Another lesson from vaccinology is that correlates of immunity may be complex, and antibody and cellular immunity are often collaborative. This point can be illustrated with reference to cytomegalovirus (CMV) [15, 16]. As in HIV, superinfection may occur in previously infected individuals, but the course of secondary infection is much less pathogenic than in non-immune subjects. This is particularly important when infection occurs in pregnancy, as the fetal outcomes after primary or secondary infection are quite different.
Antibody against CMV alone may protect against primary infection, but if infection occurs, cellular immunity is critical in controlling it. In addition, challenge dose is an important variable, and can overcome moderate levels of immunity, a fact that may apply to HIV. This was shown by challenge studies in which seronegative volunteers could be infected with 10 PFU of a low-passage CMV, whereas naturally seropositive volunteers were protected against 100 PFU, but could also be infected if the dose was raised to 1000 PFU .
Nevertheless, two vaccines in development have shown moderate ability to prevent or modify CMV infection. One is based on a live attenuated virus, and one on a glycoprotein that induces neutralizing antibody [17, 18]. Thus, the fact that superinfection has been demonstrated in some already HIV-infected people does not necessarily rule out a role for immunity in controlling disease after infection [19, 20].
Another example is immunity to smallpox after vaccinia, about which one can say that antibody is key: high titers give sterile immunity. However, as antibody wanes, infection may occur, which CD8+ T cells must control. Antibody lasts forever after vaccination and CD4+ T cells last almost forever, but CD8+ T cells disappear after about 20 years. Thus, although complete protection is temporary, protection against severe disease is permanent .
Similarities between Hepatitis C and HIV
Envelope and Core Ags
Glycosylated envelope protein
Envelope is neut. target, but hypervariable
Geographical genetic variation
High titer neutralizing Ab protects
Strong cell responses against multiple epitopes necessary for control of viremia
CD4+ cells needed to sustain CD8+ T cells
Tcm cells needed for long-term control
However, it appears that late in the infection, induction or reconstitution of cellular immune responses also correlates with recovery from chronic hepatitis C viremia [26–30]. Those cellular responses are mediated by both CD4+ and CD8+ T cells directed against non-structural as well as structural proteins; to be effective, those responses must be strong, highly avid, and directed against multiple epitopes [31–34]. Although a crucial difference between the two viruses is the lack of integration by hepatitis C in contrast to HIV, I think it is instructive to see that a chronic infection can be counteracted by standard immune responses .
So what can be said about immune protection against HIV? With regard to innate immune responses, we know that they are clearly valuable [35, 36], both immediately after infection and as adjuvants to adaptive immune responses. The question is: do they have memory? A method of maintaining elevated innate immune responses after immunization, particularly NK cells or intracellular APOBEC3G, could be valuable, although contrariwise after HIV infection, it has been reported that an HIV-induced ligand is responsible for CD4+ T cell destruction by NK cells .
On the other hand, a recent report  shows that the gene Apobec3 encodes Rfv3, which enhances neutralizing antibody responses against lentiviruses. This opens a new avenue of research to counteract its antagonist, the Vif element of HIV. In addition, soluble CD40 ligand has been shown recently to enhance HIV-specific memory T cell responses [39, 40].
Novel approaches to the design of envelope immunogens
Mimic native trimer on virion surface
Redirect immune responses to conserved conformational epitopes
Add disulfides or other amino acids to stabilize conformational epitopes
Bind envelope to CD4 or CD4-mimetic peptide
Remove carbohydrate residue or entire carbohydrate side chains
Redirect responses away from variable epitopes
Remove one or more variable loops
Add carbohydrate side chains to hide
However, short of the ideal of broad neutralization with a single antigen, it is not beyond our abilities to produce multivalent vaccines. Because of multiple serotypes or subtypes, numerous licensed vaccines are actually multivalent, including those for Human Papilloma, Influenza, Meningococcal, Pneumococcal, Polio, and Rotavirus. Moreover, every year we change the valences of influenza vaccines to match the evolution of the virus. Although this is not an ideal scenario, most years it works well; on condition that surveillance is good, and that there are regional manufacturers, it is practical to make different vaccines for different areas.
Thus, although antibodies to conserve epitopes are highly desirable, antibodies to gp120 loops that mutate and are regional in distribution may require continuous updating and regionalization of vaccine antigens (as for flu), as well as the inclusion of multiple gp 120s. Even with breakthroughs in finding conserved epitopes, I doubt that we can escape totally from having to make multivalent or regional HIV vaccines . Indeed, recent reports suggest that multivalent HIV envelopes do give broad neutralizing responses [46–49].
Does antibody protect against HIV infection? Clearly, non-human primate studies using HIVIG or monoclonal antibodies strongly support an affirmative answer [50–53]. In addition, the burden of evidence is in favor of a protective ability of maternal neutralizing antibodies in prevention of HIV transmission to the newborn . Moreover, it has been reported that neutralizing antibodies develop rapidly and in high titer after HIV-2 infection, which could explain the much slower disease progression in HIV-2 patients [55–57].
Estimates of titers of neutralizing antibodies required for sterile protection against HIV.
Indeed, booster doses are commonly needed for vaccines, even for some that are highly efficacious. They are almost always needed for inactivated vaccines, e.g. tetanus, diphtheria, and polysaccharide conjugates (exceptions are hepatitis A and hepatitis B), and are often needed for live vaccines, e.g. measles, mumps, and smallpox (exceptions are rubella and OPV). This may be an inconvenient truth, but the use of adjuvants might help prolong immunity.
The new adjuvants now available in vaccinology are legion, and they increase breadth as well as height of antibody responses. They include oil-in-water and water-in-oil emulsions, saponins, liposomes, lipopolysaccharides, cytokines, cationic polymers for DNA plasmids, mast cell activiators and numerous toll-like receptor (TLR) agonists. A recent report showed that an oil-in-water emulsion containing monophosphoryl lipid A and QS-21 substantially increased the number of primary isolates that could be neutralized in vitro by rabbit antisera [45, 65]. Much more work is needed in this area [66–68].
However, there are issues of quantity. Recently, CTL responses were measured after two conventional live vaccines, smallpox and yellow fever . In terms of percent CD8+ T cells specific to the vaccine, smallpox vaccine induced about 10% vaccinia-specific cells producing IFN-gamma, whereas yellow fever vaccine induced more than 2% yellow fever-specific cells. Compare those figures to the data from the STEP study in which only 0.5 to 1% of CD8+ T cells were specific to HIV (J McElrath, personal communication, 2008). Thus, it is legitimate to ask whether paucity of response played a role in the STEP failure.
Cellular immune responses to HIV that could be improved
Quantity of specific CD8+ cells
Polyfunctionality of CD8+ cells
Avidity of CD8+ cells
Number of epitopes seen
Intestinal homing of CD8+ cells
Increased CD4+ central memory cells
Increased CD8+ central memory cells
My goal here is not to exhaustively examine all of the important T cell responses, but rather to say that there are numerous leads with regard to improving cellular immune responses to an HIV vaccine, and that the failure of the first trial of this idea says only that the responses induced were inadequate to simulate those induced during natural infection that appear to control HIV temporarily.
Do vaccines elicit "sterile" immunity?
Depends Mucosal Presence of Antibody
Mucosal immunity is as complex as systemic immunity [100–104]. Secretory IgA may neutralize on the surface or block transcytosis . Second, the CTL population in the intestine is numerous and can kill HIV-infected cells, which is important in view of the evidence that preservation of intestinal memory CD4+ T cells contributes to a good prognosis for the subsequent course of HIV infection [106, 107]. Third, serum IgG can diffuse onto mucosal surfaces, particularly in the respiratory tract. The latter fact probably accounts for the reduction of pharyngeal carriage of encapsulated bacteria by conjugated polysaccharide vaccines, and the reduction of virus titer in the pharynx and stool of IPV vaccinees [21, 102].
I alluded to the live, orally administered rotavirus vaccine previously, and there is another lesson to be learned from the rotavirus story: rotavirus diarrhea is caused by replication of the virus in intestinal cells. There are three important proteins of the virus: two of these, vp4 and vp7, induce neutralizing antibodies, whereas the third, vp6, induces non-neutralizing antibodies and cellular immune responses.
With regard to the correlates of immunity, efficacy studies show that type-specific neutralizing antibodies are an important factor in protection. However, studies of natural immunity show that non-neutralizing as well as neutralizing antibodies to vp6 also correlate with protection [108, 109]. Moreover, studies in animals demonstrate that CTL in the intestinal lining against vp6 also have a role . Finally, measurement of serum IgA antibodies provide a surrogate of protection by the vaccine , indicating that secretory IgA in the intestinal mucosa plays a major role in that protection .
Some newer strategies for an HIV vaccine
Replicating vectors, e.g. Adenoviruses 4 and 7, CMV, Sendai, VSV, alphavirus-VSV
DNA plasmids with electroporation
Non-parenteral routes of administration: intranasal, rectal, sublingual
DNA/NYVAC prime boost regimen
Gene-driven HIV antibody
Live, attenuated HIV, e.g. Δnef, Δnef/vpr, ΔGY
(Canarypox/gp prime-boost 120 trial still ongoing in Thailand)
Of course, we must look at new vectors [117–122]. Replicating adenovirus vectors boosted by viral proteins have given promising results in prevention of SIV infection in macaques [123–125]. An interesting observation made in those studies and in other studies in macaques is the protection afforded by non-neutralizing antibodies through their action on infected cells by mechanisms such as ADCC [126–128]. This echoes the theme mentioned in relation to rotavirus.
Cytomegalovirus is under test as a replicating vector, as are measles, Sendai viruses and VSV [129, 130]. DNA plasmids are enjoying a renaissance thanks to the concomitant use of electroporation and new adjuvants [49, 131, 132]. In addition, the European Consortium, has reported polyfunctional T cell responses in humans after a DNA-NYVAC vaccinia regimen . Non-parenteral routes of administration of non-replicating vectors are also being explored . Transfer of the gene for a neutralizing antibody via an adeno-associated virus vector to vaccinees is another intriguing approach . Homology of anti-phospholipid antibodies and HIV epitopes is being explored . And some of our hearts still belong to live attenuated HIV [136–138], although this is a contentious area owing to safety concerns. One should also keep in mind that the canarypox prime, gp120 boost trial in Thailand has survived analyses for the futility of efficacy and will be reported this year, and that the prime-boost concept using a DNA prime and Ad5 boost, which gives enhanced immune responses in comparison with Ad5 alone, remains to be tested in the clinic .
In summary, I believe that an effective HIV vaccine will need to stimulate neutralizing antibodies, as well as CD4+ and CD8+ cellular responses in the blood and on the mucosa. This is hardly a novel conclusion, and it is a tall order, but the biology of the virus and the history of vaccinology tell us, respectively, that those responses are necessary and that they have been feasible to induce for previous vaccines.
At the beginning of this article, I disdained the use of optimistic or pessimistic quotations to justify opinions about the future of HIV vaccine development. I have tried to be realistic in my own assessment of the situation and I will close with one quotation, because it is definitely realistic, as everyone who has ever worked in a laboratory knows. It comes from Emile Roux, the associate of Pasteur and a brilliant scientist in his own right. He said, "Science appears calm and triumphant when it is completed; but science in the process of being done is only contradiction and torment, hope and disappointment." Let us not give up, for as Roux would agree, the goal is worth it.
This article is based on a keynote address delivered at the AIDS Vaccine Conference in Cape Town, South Africa, on 13 October 2008.
- Plotkin SA, Farquhar JD, Katz M, Buser F: Attenuation of RA 27–3 rubella virus in WI-38 human diploid cells. Am J Dis Child 1969, 118 (2) : 178–185.PubMedGoogle Scholar
- Plotkin SA, Farquhar JD, Ogra PL: Immunologic properties of RA27/3 rubella virus vaccine. Journal of American Medical Association 1973, 225: 585–590.View ArticleGoogle Scholar
- Fogel A, Gerichter CB, Barnea B, Handsher R, Heeger E: Response to experimental challenge in persons immunized with different rubella vaccines. J Pediatr 1978, 92 (1) : 26–29.PubMedView ArticleGoogle Scholar
- Polack FP: Atypical measles and enhanced respiratory syncytial virus disease (ERD) made simple. Pediatr Res 2007, 62 (1) : 111–115.PubMedView ArticleGoogle Scholar
- Polack FP, Hoffman SJ, Moss WJ, Griffin DE: Altered synthesis of interleukin-12 and type 1 and type 2 cytokinesin rhesus macaques during measles and atypical measles. J Infect Dis 2002, 185 (1) : 13–19.PubMedView ArticleGoogle Scholar
- Polack FP, Hoffman SJ, Crujeiras G, Griffin DE: A role for nonprotective complement-fixing antibodies with low avidity for measles virus in atypical measles. Nat Med 2003, 9 (9) : 1209–1213.PubMedView ArticleGoogle Scholar
- De Swart RL, Kuiken T, Timmerman HH, van AG, Hoogen BG, Vos HW, et al.: Immunization of macaques with formalin-inactivated respiratory syncytial virus (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV infection. J Virol 2002, 76 (22) : 11561–11569.PubMedView ArticleGoogle Scholar
- Tregoning JS, Yamaguchi Y, Harker J, Wang B, Openshaw PJ: The role of T cells in the enhancement of respiratory syncytial virus infection severity during adult reinfection of neonatally sensitized mice. J Virol 2008, 82 (8) : 4115–4124.PubMedView ArticleGoogle Scholar
- Intussusception among recipients of rotavirus vaccine – United States, 1998–1999MMWR Morb Mortal Wkly Rep 1999, 48 (27) : 577–581.
- Joensuu J, Koskenniemi E, Vesikari T: Symptoms associated with rhesus-human reassortant rotavirus vaccine in infants. Pediatr Infect Dis J 1998, 17 (4) : 334–340.PubMedView ArticleGoogle Scholar
- Clark HF, Offit PA, Plotkin SA, Heaton PM: The new pentavalent rotavirus vaccine composed of bovine (strain WC3) – human rotavirus reassortants. Pediatr Infect Dis J 2006, 25 (7) : 577–583.PubMedView ArticleGoogle Scholar
- Bernstein DI, Sander DS, Smith VE, Schiff GM, Ward RL: Protection from rotavirus reinfections: two-year prospective study. J Infect Dis 1991, 164: 277–283.PubMedGoogle Scholar
- Vesikari T, Matson DO, Dennehy P, Van DP, Santosham M, Rodriguez Z, et al.: Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006, 354 (1) : 23–33.PubMedView ArticleGoogle Scholar
- Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, et al.: Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006, 354 (1) : 11–22.PubMedView ArticleGoogle Scholar
- Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R: Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis 2004, 39 (2) : 233–239.PubMedView ArticleGoogle Scholar
- Plotkin SA: Is there a formula for an effective CMV vaccine? J Clin Virol 2002, 25 (Suppl 2) : S13-S21.PubMedView ArticleGoogle Scholar
- Plotkin SA, Starr SE, Friedman HM, Gonczol E, Weibel RE: Protective effects of Towne cytomegalovirus vaccine against low-passage cytomegalovirus administered as a challenge. J Infect Dis 1989, 159 (5) : 860–865.PubMedGoogle Scholar
- Pass R, Zhang C, Simpson T, et al.: Cytomegalovirus (CMV) envelope glycoprotein B (gB) vaccine in young women. [Abstract]. Infectious Diseases Society of America, (late-breaker), San Diego, CA, October 4–7, 2007 2007.Google Scholar
- Blish CA, Blay WM, Haigwood NL, Overbaugh J: Transmission of HIV-1 in the face of neutralizing antibodies. Curr HIV Res 2007, 5 (6) : 578–587.PubMedView ArticleGoogle Scholar
- Piantadosi A, Ngayo MO, Chohan B, Overbaugh J: Examination of a Second Region of the HIV Type 1 Genome Reveals Additional Cases of Superinfection. AIDS Res Hum Retroviruses 2008, 24 (9) : 1221.PubMedView ArticleGoogle Scholar
- Plotkin SA: Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis 2008, 47 (3) : 401–409.PubMedView ArticleGoogle Scholar
- Simmonds P: Genetic diversity and evolution of hepatitis C virus – 15 years on. J Gen Virol 2004, 85 (Pt 11) : 3173–3188.PubMedView ArticleGoogle Scholar
- Pestka JM, Zeisel MB, Blaser E, Schurmann P, Bartosch B, Cosset FL, et al.: Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. Proc Natl Acad Sci USA 2007, 104 (14) : 6025–6030.PubMedView ArticleGoogle Scholar
- Houghton M, Abrignani S: Prospects for a vaccine against the hepatitis C virus. Nature 2005, 436 (7053) : 961–966.PubMedView ArticleGoogle Scholar
- Von Hahn T, Yoon JC, Alter H, Rice CM, Rehermann B, Balfe P, et al.: Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo. Gastroenterology 2007, 132 (2) : 667–678.View ArticleGoogle Scholar
- Elmowalid GA, Qiao M, Jeong SH, Borg BB, Baumert TF, Sapp RK, et al.: Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees. Proc Natl Acad Sci USA 2007, 104 (20) : 8427–8432.PubMedView ArticleGoogle Scholar
- Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV: Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 2001, 194 (10) : 1395–1406.PubMedView ArticleGoogle Scholar
- Thimme R, Neumann-Haefelin C, Boettler T, Blum HE: Adaptive immune responses to hepatitis C virus: from viral immunobiology to a vaccine. Biol Chem 2008, 389 (5) : 457–67.PubMedView ArticleGoogle Scholar
- Lechner F, Wong DK, Dunbar PR, Chapman R, Chung RT, Dohrenwend P, et al.: Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 2000, 191 (9) : 1499–1512.PubMedView ArticleGoogle Scholar
- Bassett SE, Guerra B, Brasky K, Miskovsky E, Houghton M, Klimpel GR, et al.: Protective immune response to hepatitis C virus in chimpanzees rechallenged following clearance of primary infection. Hepatology 2001, 33 (6) : 1479–1487.PubMedView ArticleGoogle Scholar
- Shoukry NH, Grakoui A, Houghton M, Chien DY, Ghrayeb J, Reimann KA, et al.: Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection. J Exp Med 2003, 197 (12) : 1645–1655.PubMedView ArticleGoogle Scholar
- Yerly D, Heckerman D, Allen TM, Chisholm JV III, Faircloth K, Linde CH, et al.: Increased cytotoxic T-lymphocyte epitope variant cross-recognition and functional avidity are associated with hepatitis C virus clearance. J Virol 2008, 82 (6) : 3147–3153.PubMedView ArticleGoogle Scholar
- Strickland GT, El-Kamary SS, Klenerman P, Nicosia A: Hepatitis C vaccine: supply and demand. Lancet Infect Dis 2008, 8 (6) : 379–386.PubMedView ArticleGoogle Scholar
- Lin Y, Kwon T, Polo J, Zhu YF, Coates S, Crawford K, et al.: Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5. J Virol 2008, 82 (15) : 7492–7503.PubMedView ArticleGoogle Scholar
- Lehner T, Wang Y, Pido-Lopez J, Whittall T, Bergmeier LA, Babaahmady K: The emerging role of innate immunity in protection against HIV-1 infection. Vaccine 2008, 26 (24) : 2997–3001.PubMedView ArticleGoogle Scholar
- Pido-Lopez J, Whittall T, Wang Y, Bergmeier LA, Babaahmady K, Singh M, et al.: Stimulation of cell surface CCR5 and CD40 molecules by their ligands or by HSP70 up-regulates APOBEC3G expression in CD4(+) T cells and dendritic cells. J Immunol 2007, 178 (3) : 1671–1679.PubMedGoogle Scholar
- Vieillard V, Le GR, Dausset J, Debre P: A vaccine strategy against AIDS: an HIV gp41 peptide immunization prevents NKp44L expression and CD4+ T cell depletion in SHIV-infected macaques. Proc Natl Acad Sci USA 2008, 105 (6) : 2100–2104.PubMedView ArticleGoogle Scholar
- Santiago ML, Montano M, Benitez R, Messer RJ, Yonemoto W, Chesebro B, et al.: Apobec3 encodes Rfv3, a gene influencing neutralizing antibody control of retrovirus infection. Science 2008, 321 (5894) : 1343–1346.PubMedView ArticleGoogle Scholar
- Miconnet I, Pantaleo G: A soluble hexameric form of CD40 ligand activates human dendritic cells and augments memory T cell response. Vaccine 2008, 26 (32) : 4006–4014.PubMedView ArticleGoogle Scholar
- Liu J, Yu Q, Stone GW, Yue FY, Ngai N, Jones RB, et al.: CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals. Vaccine 2008, 26 (32) : 4062–4072.PubMedView ArticleGoogle Scholar
- Johnston MI, Fauci AS: An HIV vaccine – evolving concepts. N Engl J Med 2007, 356 (20) : 2073–2081.PubMedView ArticleGoogle Scholar
- Burioni R, Mancini N, De MD, Clementi N, Perotti M, Nitti G, et al.: Anti-HIV-1 response elicited in rabbits by anti-idiotype monoclonal antibodies mimicking the CD4-binding site. PLoS ONE 2008, 3 (10) : e3423.PubMedView ArticleGoogle Scholar
- Babaahmady K, Bergmeier LA, Lehner T: Combining human antisera to human leukocyte antigens, HIVgp120 and 70 kDa heat shock protein results in broadly neutralizing activity to HIV-1. AIDS 2008, 22 (11) : 1267–1276.PubMedView ArticleGoogle Scholar
- Lewis AD, Chen R, Montefiori DC, Johnson PR, Clark KR: Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer. J Virol 2002, 76 (17) : 8769–8775.PubMedView ArticleGoogle Scholar
- Karlsson Hedestam GB, Fouchier RA, Phogat S, Burton DR, Sodroski J, Wyatt RT: The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus. Nat Rev Microbiol 2008, 6 (2) : 143–155.PubMedView ArticleGoogle Scholar
- Graham BS, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, et al.: Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis 2006, 194 (12) : 1650–1660.PubMedView ArticleGoogle Scholar
- Seaman MS, Xu L, Beaudry K, Martin KL, Beddall MH, Miura A, et al.: Multiclade human immunodeficiency virus type 1 envelope immunogens elicit broad cellular and humoral immunity in rhesus monkeys. J Virol 2005, 79 (5) : 2956–2963.PubMedView ArticleGoogle Scholar
- Wang S, Pal R, Mascola JR, Chou TH, Mboudjeka I, Shen S, et al.: Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus protein boosting approach are effective in generating neutralizing antibodies against primary human immunodeficiency virus type 1 isolates from subtypes A, B, C, D and E. Virology 2006, 350 (1) : 34–47.PubMedView ArticleGoogle Scholar
- Wang S, Kennedy JS, West K, Montefiori DC, Coley S, Lawrence J, et al.: Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers. Vaccine 2008, 26 (31) : 3947–3957.PubMedView ArticleGoogle Scholar
- Mascola JR, Lewis MG, Stiegler G, Harris D, VanCott TC, Hayes D, et al.: Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6 PD by passive transfer of neutralizing antibodies. J Virol 1999, 73 (5) : 4009–4018.PubMedGoogle Scholar
- Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB, Hanson CE, et al.: Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 2000, 6 (2) : 207–210.PubMedView ArticleGoogle Scholar
- Mascola JR: Passive transfer studies to elucidate the role of antibody-mediated protection against HIV-1. Vaccine 2002, 20 (15) : 1922–1925.PubMedView ArticleGoogle Scholar
- Yamamoto H, Kawada M, Takeda A, Igarashi H, Matano T: Post-infection immunodeficiency virus control by neutralizing antibodies. PLoS ONE 2007, 2 (6) : e540.PubMedView ArticleGoogle Scholar
- Barin F, Jourdain G, Brunet S, Ngo-Giang-Huong N, Weerawatgoompa S, Karnchanamayul W, et al.: Revisiting the role of neutralizing antibodies in mother-to-child transmission of HIV-1. J Infect Dis 2006, 193 (11) : 1504–1511.PubMedView ArticleGoogle Scholar
- Bjorling E, Scarlatti G, von GA, Albert J, Biberfeld G, Chiodi F, et al.: Autologous neutralizing antibodies prevail in HIV-2 but not in HIV-1 infection. Virology 1993, 193 (1) : 528–530.PubMedView ArticleGoogle Scholar
- Shi Y, Brandin E, Vincic E, Jansson M, Blaxhult A, Gyllensten K, et al.: Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. J Gen Virol 86 (Pt 12) : 3385–3396.
- Leligdowicz A, Rowland-Jones S: Tenets of protection from progression to AIDS: lessons from the immune responses to HIV-2 infection. Expert Rev Vaccines 2008, 7 (3) : 319–331.PubMedView ArticleGoogle Scholar
- Trkola A, Kuster H, Rusert P, von WV, Leemann C, Weber R, et al.: In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers. J Virol 2008, 82 (3) : 1591–1599.PubMedView ArticleGoogle Scholar
- Trkola A, Kuster H, Rusert P, Joos B, Fischer M, Leemann C, et al.: Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med 2005, 11 (6) : 615–622.PubMedView ArticleGoogle Scholar
- Parren PW, Marx PA, Hessell AJ, Luckay A, Harouse J, Cheng-Mayer C, et al.: Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol 2001, 75 (17) : 8340–8347.PubMedView ArticleGoogle Scholar
- Nishimura Y, Igarashi T, Haigwood N, Sadjadpour R, Plishka RJ, Buckler-White A, et al.: Determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies. J Virol 2002, 76 (5) : 2123–2130.PubMedView ArticleGoogle Scholar
- Smith DM, Strain MC, Frost SD, Pillai SK, Wong JK, Wrin T, et al.: Lack of neutralizing antibody response to HIV-1 predisposes to superinfection. Virology 2006, 355 (1) : 1–5.PubMedView ArticleGoogle Scholar
- Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, et al.: Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 2008, 105 (21) : 7552–7557.PubMedView ArticleGoogle Scholar
- Miller CJ, Li Q, Abel K, Kim EY, Ma ZM, Wietgrefe S, et al.: Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 2005, 79 (14) : 9217–9227.PubMedView ArticleGoogle Scholar
- Zhang PF, Cham F, Dong M, Choudhary A, Bouma P, Zhang Z, et al.: Extensively cross-reactive anti-HIV-1 neutralizing antibodies induced by gp140 immunization. Proc Natl Acad Sci USA 2007, 104 (24) : 10193–10198.PubMedView ArticleGoogle Scholar
- Deeks SG, Schweighardt B, Wrin T, Galovich J, Hoh R, Sinclair E, et al.: Neutralizing antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus (HIV) infection: evidence for a constraint on the ability of HIV to completely evade neutralizing antibody responses. J Virol 2006, 80 (12) : 6155–6164.PubMedView ArticleGoogle Scholar
- Sattentau Q: Correlates of antibody-mediated protection against HIV infection. Current Opinion in HIV and AIDS 2008, 3: 368–374.PubMedView ArticleGoogle Scholar
- Brown BK, Wieczorek L, Sanders-Buell E, Rosa BA, Robb ML, Birx DL, et al.: Cross-clade neutralization patterns among HIV-1 strains from the six major clades of the pandemic evaluated and compared in two different models. Virology 2008, 375 (2) : 529–538.PubMedView ArticleGoogle Scholar
- Kuroda MJ, Schmitz JE, Charini WA, Nickerson CE, Lifton MA, Lord CI, et al.: Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys. J Immunol 1999, 162 (9) : 5127–5133.PubMedGoogle Scholar
- Wilson NA, Reed J, Napoe GS, Piaskowski S, Szymanski A, Furlott J, et al.: Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239. J Virol 2006, 80 (12) : 5875–5885.PubMedView ArticleGoogle Scholar
- Deeks SG, Walker BD: Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 2007, 27 (3) : 406–416.PubMedView ArticleGoogle Scholar
- Hess C, Altfeld M, Thomas SY, Addo MM, Rosenberg ES, Allen TM, et al.: HIV-1 specific CD8+ T cells with an effector phenotype and control of viral replication. Lancet 2004, 363 (9412) : 863–866.PubMedView ArticleGoogle Scholar
- Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, et al.: Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 1999, 283 (5403) : 857–860.PubMedView ArticleGoogle Scholar
- Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB: Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 1994, 68 (9) : 6103–6110.PubMedGoogle Scholar
- Sacha JB, Chung C, Rakasz EG, Spencer SP, Jonas AK, Bean AT, et al.: Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression. J Immunol 2007, 178 (5) : 2746–2754.PubMedGoogle Scholar
- Lifson JD, Rossio JL, Piatak M Jr, Parks T, Li L, Kiser R, et al.: Role of CD8(+) lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. J Virol 2001, 75 (21) : 10187–10199.PubMedView ArticleGoogle Scholar
- Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, et al.: HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006, 107 (12) : 4781–4789.PubMedView ArticleGoogle Scholar
- Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, Rathod A, et al.: Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis 2008, 197 (4) : 563–571.PubMedView ArticleGoogle Scholar
- Saez-Cirion A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A, Boufassa F, et al.: HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA 2007, 104 (16) : 6776–6781.PubMedView ArticleGoogle Scholar
- Piacentini L, Fenizia C, Naddeo V, Clerici M: Not just sheer luck! Immune correlates of protection against HIV-1 infection. Vaccine 2008, 26 (24) : 3002–3007.PubMedView ArticleGoogle Scholar
- Potter SJ, Lacabaratz C, Lambotte O, Perez-Patrigeon S, Vingert B, Sinet M, et al.: Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers: an ANRS EP36 study. J Virol 2007, 81 (24) : 13904–13915.PubMedView ArticleGoogle Scholar
- Chase AJ, Yang HC, Zhang H, Blankson JN, Siliciano RF: Preservation of FoxP3+ regulatory T cells in the peripheral blood of human immunodeficiency virus type 1-infected elite suppressors correlates with low CD4+ T-cell activation. J Virol 2008, 82 (17) : 8307–8315.PubMedView ArticleGoogle Scholar
- Kulkarni PS, Butera ST, Duerr AC: Resistance to HIV-1 infection: lessons learned from studies of highly exposed persistently seronegative (HEPS) individuals. AIDS Rev 2003, 5 (2) : 87–103.PubMedGoogle Scholar
- Miller JD, Most RG, Akondy RS, Glidewell JT, Albott S, Masopust D, et al.: Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity 2008, 28 (5) : 710–722.PubMedView ArticleGoogle Scholar
- Turk G, Gherardi MM, Laufer N, Saracco M, Luzzi R, Cox JH, et al.: Magnitude, breadth, and functional profile of T-cell responses during human immunodeficiency virus primary infection with B and BF viral variants. J Virol 2008, 82 (6) : 2853–2866.PubMedView ArticleGoogle Scholar
- Critchfield JW, Lemongello D, Walker DH, Garcia JC, Asmuth DM, Pollard RB, et al.: Multifunctional human immunodeficiency virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. J Virol 2007, 81 (11) : 5460–5471.PubMedView ArticleGoogle Scholar
- Kawada M, Igarashi H, Takeda A, Tsukamoto T, Yamamoto H, Dohki S, et al.: Involvement of multiple epitope-specific cytotoxic T-lymphocyte responses in vaccine-based control of simian immunodeficiency virus replication in rhesus macaques. J Virol 2006, 80 (4) : 1949–1958.PubMedView ArticleGoogle Scholar
- Sun Y, Santra S, Schmitz JE, Roederer M, Letvin NL: Magnitude and quality of vaccine-elicited T-cell responses in the control of immunodeficiency virus replication in rhesus monkeys. J Virol 2008, 82 (17) : 8812–8819.PubMedView ArticleGoogle Scholar
- Daucher M, Price DA, Brenchley JM, Lamoreaux L, Metcalf JA, Rehm C, et al.: Virological outcome after structured interruption of antiretroviral therapy for human immunodeficiency virus infection is associated with the functional profile of virus-specific CD8+ T cells. J Virol 2008, 82 (8) : 4102–4114.PubMedView ArticleGoogle Scholar
- Bennett MS, Ng HL, Dagarag M, Ali A, Yang OO: Epitope-dependent avidity thresholds for cytotoxic T-lymphocyte clearance of virus-infected cells. J Virol 2007, 81 (10) : 4973–4980.PubMedView ArticleGoogle Scholar
- Belyakov IM, Isakov D, Zhu Q, Dzutsev A, Berzofsky JA: A novel functional CTL avidity/activity compartmentalization to the site of mucosal immunization contributes to protection of macaques against simian/human immunodeficiency viral depletion of mucosal CD4+ T cells. J Immunol 2007, 178 (11) : 7211–7221.PubMedGoogle Scholar
- Kawada M, Tsukamoto T, Yamamoto H, Takeda A, Igarashi H, Watkins DI, et al.: Long-term control of simian immunodeficiency virus replication with central memory CD4+ T-cell preservation after nonsterile protection by a cytotoxic T-lymphocyte-based vaccine. J Virol 2007, 81 (10) : 5202–5211.PubMedView ArticleGoogle Scholar
- Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, et al.: Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med 2007, 13 (1) : 100–106.PubMedView ArticleGoogle Scholar
- Santra S, Korber BT, Muldoon M, Barouch DH, Nabel GJ, Gao F, et al.: A centralized gene-based HIV-1 vaccine elicits broad cross-clade cellular immune responses in rhesus monkeys. Proc Natl Acad Sci USA 2008, 105 (30) : 10489–10494.PubMedView ArticleGoogle Scholar
- Brenchley JM, Paiardini M, Knox KS, Asher AI, Cervasi B, Asher TE, et al.: Differential Th17 CD4 T cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 2008.
- Sun Y, Schmitz JE, Buzby AP, Barker BR, Rao SS, Xu L, et al.: Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. J Virol 2006, 80 (22) : 10950–10956.PubMedView ArticleGoogle Scholar
- Ruggiero E, Bona R, Muratori C, Federico M: Virological consequences of early events following cell-cell contact between human immunodeficiency virus type 1-infected and uninfected CD4+ cells. J Virol 2008, 82 (16) : 7773–7789.PubMedView ArticleGoogle Scholar
- Chen RT, Markowitz LE, Albrecht P, Stewart JA, Mofenson LM, Preblud SR, et al.: Measles antibody: reevaluation of protective titers. J Infect Dis 1990, 162 (5) : 1036–1042.PubMedGoogle Scholar
- Belshe RB, Gruber WC, Mendelman PM, Mehta HB, Mahmood K, Reisinger K, et al.: Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine. J Infect Dis 2000, 181 (3) : 1133–1137.PubMedView ArticleGoogle Scholar
- Haynes BF, Shattock RJ: Critical issues in mucosal immunity for HIV-1 vaccine development. J Allergy Clin Immunol 2008, 122 (1) : 3–9.PubMedView ArticleGoogle Scholar
- Girard MP, Bansal GP, Pedroza-Martins L, Dodet B, Mehra V, Schito M, et al.: Mucosal immunity and HIV/AIDS vaccines: Report of an International Workshop, 28–30 October 2007. Vaccine 2008, 26 (32) : 3969–3977.PubMedView ArticleGoogle Scholar
- Bouvet JP, Fischetti VA: Diversity of antibody-mediated immunity at the mucosal barrier. Infect Immun 1999, 67 (6) : 2687–2691.PubMedGoogle Scholar
- Shattock RJ, Haynes BF, Pulendran B, Flores J, Esparza J: Improving defences at the portal of HIV entry: mucosal and innate immunity. PLoS Med 2008, 5 (4) : e81.PubMedView ArticleGoogle Scholar
- Brandtzaeg P: Induction of secretory immunity and memory at mucosal surfaces. Vaccine 2007, 25 (30) : 5467–5484.PubMedView ArticleGoogle Scholar
- Mestecky J, Jackson S, Moldoveanu Z, Nesbit LR, Kulhavy R, Prince SJ, et al.: Paucity of antigen-specific IgA responses in sera and external secretions of HIV-type 1-infected individuals. AIDS Res Hum Retroviruses 2004, 20 (9) : 972–988.PubMedView ArticleGoogle Scholar
- Veazey RS, DeMaria M, Chalifoux LV, Shvetz DE, Pauley DR, Knight HL, et al.: Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 1998, 280 (5362) : 427–431.PubMedView ArticleGoogle Scholar
- Ling B, Veazey RS, Hart M, Lackner AA, Kuroda M, Pahar B, et al.: Early restoration of mucosal CD4 memory CCR5 T cells in the gut of SIV-infected rhesus predicts long term non-progression. AIDS 2007, 21 (18) : 2377–2385.PubMedView ArticleGoogle Scholar
- Kallewaard NL, McKinney BA, Gu Y, Chen A, Prasad BV, Crowe JE Jr: Functional maturation of the human antibody response to rotavirus. J Immunol 2008, 180 (6) : 3980–3989.PubMedGoogle Scholar
- Garaicoechea L, Olichon A, Marcoppido G, Wigdorovitz A, Mozgovoj M, Saif L, et al.: Llama-derived single-chain antibody fragments directed to rotavirus VP6 protein possess broad neutralizing activity in vitro and confer protection against diarrhea in mice. J Virol 2008, 82 (19) : 9753–9764.PubMedView ArticleGoogle Scholar
- Yuan L, Wen K, Azevedo MS, Gonzalez AM, Zhang W, Saif LJ: Virus-specific intestinal IFN-gamma producing T cell responses induced by human rotavirus infection and vaccines are correlated with protection against rotavirus diarrhea in gnotobiotic pigs. Vaccine 2008, 26 (26) : 3322–3331.PubMedView ArticleGoogle Scholar
- Clark HF, Offit PA, Vidor E: Rotavirus Vaccines. In Vaccines. Edited by: Plotkin S, Orenstein WA, Offit PA. Saunders-Elsevier; 2008:715–734.Google Scholar
- Azevedo MS, Yuan L, Iosef C, Chang KO, Kim Y, Nguyen TV, et al.: Magnitude of serum and intestinal antibody responses induced by sequential replicating and nonreplicating rotavirus vaccines in gnotobiotic pigs and correlation with protection. Clin Diagn Lab Immunol 2004, 11 (1) : 12–20.PubMedGoogle Scholar
- Mattapallil JJ, Roederer M: Mucosa and vaccine-induced immune protection in nonhuman primates. Current Opinion in HIV and AIDS 2008, 3: 387–392.PubMedView ArticleGoogle Scholar
- Hirbod T, Kaul R, Reichard C, Kimani J, Ngugi E, Bwayo JJ, et al.: HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers. AIDS 2008, 22 (6) : 727–735.PubMedView ArticleGoogle Scholar
- Nardelli-Haefliger D, Lurati F, Wirthner D, Spertini F, Schiller JT, Lowy DR, et al.: Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine. Vaccine 2005, 23 (28) : 3634–3641.PubMedView ArticleGoogle Scholar
- Cuburu N, Kweon MN, Song JH, Hervouet C, Luci C, Sun JB, et al.: Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine 2007, 25 (51) : 8598–8610.PubMedView ArticleGoogle Scholar
- Vaine M, Wang S, Crooks ET, Jiang P, Montefiori DC, Binley J, et al.: Improved induction of antibodies against key neutralizing epitopes by human immunodeficiency virus type 1 gp120 DNA prime-protein boost vaccination compared to gp120 protein-only vaccination. J Virol 2008, 82 (15) : 7369–7378.PubMedView ArticleGoogle Scholar
- Pan CH, Nair N, Adams RJ, Zink MC, Lee EY, Polack FP, et al.: Dose-dependent protection against or exacerbation of disease by a polylactide glycolide microparticle-adsorbed, alphavirus-based measles virus DNA vaccine in rhesus macaques. Clin Vaccine Immunol 2008, 15 (4) : 697–706.PubMedView ArticleGoogle Scholar
- Pal R, Kalyanaraman VS, Nair BC, Whitney S, Keen T, Hocker L, et al.: Immunization of rhesus macaques with a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine elicits protective antibody response against simian human immunodeficiency virus of R5 phenotype. Virology 2006, 348 (2) : 341–353.PubMedView ArticleGoogle Scholar
- Matano T, Kobayashi M, Igarashi H, Takeda A, Nakamura H, Kano M, et al.: Cytotoxic T lymphocyte-based control of simian immunodeficiency virus replication in a preclinical AIDS vaccine trial. J Exp Med 2004, 199 (12) : 1709–1718.PubMedView ArticleGoogle Scholar
- Malkevitch NV, Patterson LJ, Aldrich MK, Wu Y, Venzon D, Florese RH, et al.: Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses. Virology 2006, 353 (1) : 83–98.PubMedView ArticleGoogle Scholar
- Buonaguro L, Devito C, Tornesello ML, Schroder U, Wahren B, Hinkula J, et al.: DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity. Vaccine 2007, 25 (32) : 5968–5977.PubMedView ArticleGoogle Scholar
- Robert-Guroff M: Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol 2007, 18 (6) : 546–556.PubMedView ArticleGoogle Scholar
- Patterson LJ, Robert-Guroff M: Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development. Expert Opin Biol Ther 2008, 8 (9) : 1347–1363.PubMedView ArticleGoogle Scholar
- Patterson LJ, Beal J, Demberg T, Florese RH, Malkevich N, Venzon D, et al.: Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques. Virology 2008, 374 (2) : 322–337.PubMedView ArticleGoogle Scholar
- Burton DR: Antibodies, viruses and vaccines. Nat Rev Immunol 2002, 2 (9) : 706–713.PubMedView ArticleGoogle Scholar
- Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, Bakker JM, et al.: Fc receptor but not complement binding is important in antibody protection against HIV. Nature 2007, 449 (7158) : 101–104.PubMedView ArticleGoogle Scholar
- Weinhold KJ: Anti-HIV-1 ADCC: clinical and therapeutic implications. Biotechnol Ther 1991, 2 (1–2) : 147–157.PubMedGoogle Scholar
- Koff WC, Parks CL, Berkhout B, Ackland J, Noble S, Gust ID: Replicating viral vectors as HIV vaccines Summary Report from IAVI Sponsored Satellite Symposium, International AIDS Society Conference, July 22, 2007. Biologicals 2008.
- Kawada M, Tsukamoto T, Yamamoto H, Iwamoto N, Kurihara K, Takeda A, et al.: Gag-specific cytotoxic T-lymphocyte-based control of primary simian immunodeficiency virus replication in a vaccine trial. J Virol 2008, 82 (20) : 10199–10206.PubMedView ArticleGoogle Scholar
- Kutzler MA, Weiner DB: DNA vaccines: ready for prime time? Nat Rev Genet 2008, 9 (10) : 776–788.PubMedView ArticleGoogle Scholar
- Lu S: Immunogenicity of DNA vaccines in humans: it takes two to tango. Hum Vaccin 2008, 4 (6) : 449–452.PubMedGoogle Scholar
- Harari A, Bart PA, Stohr W, Tapia G, Garcia M, Medjitna-Rais E, et al.: An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses. J Exp Med 2008, 205 (1) : 63–77.PubMedView ArticleGoogle Scholar
- Stahl-Hennig C, Kuate S, Franz M, Suh YS, Stoiber H, Sauermann U, et al.: Atraumatic oral spray immunization with replication-deficient viral vector vaccines. J Virol 2007, 81 (23) : 13180–13190.PubMedView ArticleGoogle Scholar
- Alam SM, McAdams M, Boren D, Rak M, Scearce RM, Gao F, et al.: The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes. J Immunol 2007, 178 (7) : 4424–4435.PubMedGoogle Scholar
- Koff WC, Johnson PR, Watkins DI, Burton DR, Lifson JD, Hasenkrug KJ, et al.: HIV vaccine design: insights from live attenuated SIV vaccines. Nat Immunol 2006, 7 (1) : 19–23.PubMedView ArticleGoogle Scholar
- Mansfield K, Lang SM, Gauduin MC, Sanford HB, Lifson JD, Johnson RP, et al.: Vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the periphery. J Virol 2008, 82 (8) : 4135–4148.PubMedView ArticleGoogle Scholar
- Nolan KM, Jordan AP, Hoxie JA: Effects of partial deletions within the human immunodeficiency virus type 1 V3 loop on coreceptor tropism and sensitivity to entry inhibitors. J Virol 2008, 82 (2) : 664–673.PubMedView ArticleGoogle Scholar
- Cox KS, Clair JH, Prokop MT, Sykes KJ, Dubey SA, Shiver JW, et al.: DNA gag/adenovirus type 5 (Ad5) gag and Ad5 gag/Ad5 gag vaccines induce distinct T-cell response profiles. J Virol 2008, 82 (16) : 8161–8171.PubMedView ArticleGoogle Scholar
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