Modest HIV protection confirmed

With the full results of the Thai HIV vaccine trial released this morning (October 20) at a conference in Paris, the HIV/AIDS research community can breathe a sigh of relief: The vaccine candidate does appear to offer a real, albeit modest, level of protection against HIV infection. Human Immunodeficiency VirusImage: Wikimedia commons, NIAID"

By | October 20, 2009

With the full results of the Thai HIV vaccine trial released this morning (October 20) at a conference in Paris, the HIV/AIDS research community can breathe a sigh of relief: The vaccine candidate does appear to offer a real, albeit modest, level of protection against HIV infection.
Human Immunodeficiency Virus
Image: Wikimedia commons,
"What we saw today was a more complete presentation of different types of analyses that were done, [and] the scientific conclusions are as they were described earlier," said virologist linkurl:Gary Nabel,; director of the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., who did not participate in the research. "This really is a landmark study for HIV vaccine research." After the linkurl:preliminary results were released; late last month, linkurl:many raised concerns; about whether the 31% decrease in HIV infection risk shown by the vaccine candidate was genuine or a statistical anomaly. The doubts were in part fueled by hints of additional analyses that yielded weaker and non-significant effects. The full data, presented at the meeting and linkurl:published today in the New England Journal of Medicine (NEJM),; alleviated some of those uncertainties by showing the same trend in three different analyses -- the intent to treat (ITT), which included all 16,402 subjects; the modified intent to treat (MITT), which excluded seven individuals who were infected with HIV before the trial even began (and was the only analysis made public last month); and the per protocol analysis, which excluded any subject who did not receive all six doses of the vaccine within the correct time periods (about 25% of subjects) as well as any individuals who became infected over the course of the study (about 31% of subjects). Although the MITT analysis was the only one that reached statistical significance, it "was the most appropriate," and "all three analyses are qualitatively similar," said infectious disease epidemiologist linkurl:Seth Berkley,; CEO of the International AIDS Vaccine Initiative (IAVI), who was not involved in the study. "It's unfortunate that the controversy occurred, [but] now with all the data in front of us, [we can see that] there is a signal there." What's important now, researchers agree, is learning as much as possible from the results of this trial. Two "intriguing" trends in particular that emerged during today's meeting deserve a closer look, Berkley said. First, the vaccine seemed to provide a higher level of protection early that waned over time, and second, that protection appeared to be stronger for low and moderate risk groups, as opposed to the high risk group. "All those things make sense if you think about the pathogenesis of HIV," said viral immunologist linkurl:Barney Graham; of the VRC, who was not involved in the research. "Typically in an HIV infection you're only infected with one virus. [These results suggest] we may be right on the threshold of being able to control a single virion, but we may not be close to controlling a group of virions -- for example, in IV drug users, or people with genital ulcers." Another area that warrants further investigation is the mechanism behind the vaccine's effectiveness. The vaccine is a combination of two HIV vaccine candidates -- one that showed no effect and another that was never tested in an efficacy trial. "The combination of the two worked," Berkley said, "and so the question is why? What's the mechanism?" "I think this has inspired the field and given hope that it is possible to give protection in humans," Berkley said. "If a poor vaccine and a weakly immunogenic vaccine together can provide protection, then [developing an effective vaccine] may be easier than we originally thought." In addition, the trial revealed no difference in viral load or CD4 counts of infected individuals, suggesting that "those immune responses that might be able to initially prevent HIV infection and those that modulate [the virus] once you have become infected might be quite different," linkurl:Colonel Nelson Michael; of the Walter Reed Army Institute of Research and the US Military HIV Research Program (MHRP) said during a press conference this morning. The trial's collaborators are assembling four advisory committees "to interpret the results and plan future [vaccine trials]," said Michael, who is a coauthor on the NEJM paper. "We're looking forward to the rich discussion [about the results] that has already begun."
**__Related stories:__***linkurl:Hubbub brews for HIV vax data;
[12th October 2009]*linkurl:HIV vax testers react to Thai trial;
[24th September 2009]*linkurl:New wrinkle for HIV vaccine;
[25th February 2009]


Avatar of: Rob C

Rob C

Posts: 1

October 20, 2009

Very exciting. Are those involved optimistic that these developments could lead to more complete vaccination?
Avatar of: Jesse Creel

Jesse Creel

Posts: 12

October 21, 2009

I wonder if partnering of CD4 and NK Cells spoken to in this Polly Matzigner article and related commentary might have something to do with observed efficacy in the RV-144 ALVAC Prime AIDSVAX Boost HIV Vaccine Thailand trial.\n\n\nJesse Creel\nVaccine Research Advocate\n===============================================\nMMUNOBIOLOGY\nCD4 cells can be more efficient at tumor rejection than CD8 cells\nAinhoa Perez-Diez1, Nathalie T. Joncker3, Kyungho Choi2, William F. N. Chan4, Colin C. Anderson4,5, Olivier Lantz3, and Polly Matzinger1\n\nFrom the 1 Ghost Lab 2 Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; 3 Laboratoire d'Immunologie and U520 Institut National de la Santé et de la Recherche Médicale, Institute Curie, Paris, France; and Departments of 4 Medical Microbiology & Immunology and 5 Surgery, University of Alberta, Edmonton, AB, Canada\n\nResearchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current "gold standard" effector cell in tumor immunotherapy.\n=================================================\n\nComment on Perez-Diez et al, page 5346\nAntitumor T-cell wars: do CD4s\noutwit CD8s?\n\nIgnacio Melero UNIVERSIDAD DE NAVARRA\n\nIn this issue of Blood, Perez-Diez and colleagues report the findings of a series of side by-side comparisons on the ability of monoclonalCD4 andCD8 Tcells to reject\ntransplanted tumors expressing the cognate antigen. Their model focuses on tumors expressing male-exclusive minor histocompatibility antigens and female T-cell receptor\n(TCR) transgenic mice, whose onlyTCRsare specific for male antigens presented either byMHCclass I or class II molecules.\n
Avatar of: Joseph Popolow

Joseph Popolow

Posts: 1

October 22, 2009

This relatively underknown, underowned, Biotech-Nanotechnology Company is working on an approach to reduce the HIV problem, on a worldwide bases.\n Please review and comment. Thank you!

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