Breakthrough Infections during Phase 1 and 2 Prime‐Boost HIV‐1 Vaccine Trials with Canarypox Vectors (ALVAC) and Booster Dose of Recombinant gp120 or gp160

University of Rochester, Rochester, New York, United States
The Journal of Infectious Diseases (Impact Factor: 6). 09/2004; 190(5):903-7. DOI: 10.1086/423284
Source: PubMed


Candidate human immunodeficiency virus (HIV)-1 vaccines that elicit cytotoxic T lymphocytes may modulate HIV infection, requiring
a prototype evaluation to assess participants who become infected with HIV. Of 1497 participants in canarypox HIV-1 vaccine
prime-boost trials, 28 (1.9%) acquired HIV-1 infection after vaccination. Median plasma HIV-1 RNA levels (vaccinees, 4.78
log10 copies/mL; placebo recipients, 4.27 log10 copies/mL) and CD4 cell counts (vaccinees, 552 cells/mm3; placebo recipients, 657 cells/mm3) before administration of antiretroviral therapy (ART) and time to a composite end point (plasma HIV-1 RNA level >55,000
copies/mL, CD4 cell count <350 cells/mm3, or initiation of ART) did not differ significantly between vaccinees and placebo recipients (P = .4, P = .1, and P = .7, respectively). Persons who acquire HIV-1 infection while enrolled in HIV-1 vaccine trials can be successfully followed
after infection, to determine whether vaccines alter the course of HIV-1 infection.

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    • "The model, which sub-divides the HIV-infected population into counselled, non-counselled and treated individuals, also allows for HIV transmission by individuals with clinical symptoms of AIDS (in addition to transmission by infected individuals without AIDS symptoms). Although many HIV transmission models are built on the assumption that individuals in the AIDS stage do not transmit HIV (on the assumption that these individuals are too sick to partake in sexual activity), epidemiological evidence supports the hypothesis that AIDS patients are capable of, and do engage in, risky behavior such as having multiple sexual partners or inconsistent condom use [21] [29] [31]. Thus, it is plausible to incorporate the contribution of these individuals in the transmission dynamics of HIV/AIDS. "

    Full-text · Article · Oct 2010
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    • "Unfortunately, this was not the case in any of the trials finished until now. Not only the vaccines did not provide any protection against HIV-1 infection, but also there was no difference between the vaccine and placebo arms as regards the progression of HIV disease in breakthrough infection [3] [5] [6]. "
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    ABSTRACT: Considering recent HIV vaccine failures, the authors believe that it would be most important to find new targets for vaccine-induced immunity, and to analyze the data from previous trials, using an innovative approach. In their review article, the authors briefly summarize the significance of the antibody-dependent enhancement of infection in different viral diseases and discuss role of these types of antibodies as the obstacles for vaccine development. Findings which indicate that complement-mediated antibody-dependent enhancement (C-ADE) is present also in HIV-infected patients, are summarized. Previous results of the authors, suggesting that C-ADE plays a very important role in the progression of HIV infection are described. Data reflecting that enhancing antibodies may develop even in vaccinated animals and human volunteers, and may be responsible for the paradoxical results obtained in some subgroups of vaccinees are discussed. Finally, based on their hypothesis, the authors offer some suggestions for the future development of vaccines.
    Full-text · Article · Jul 2008 · Vaccine
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    • "The failure of the VAXGEN vaccine trials demonstrates that it will be difficult to protect individuals from HIV challenge with antibody-based vaccines. The infection of 28 volunteers vaccinated with canarypox shows that it will also be difficult for vaccines that induce HIV-specific CD8 responses to protect against HIV challenge (Lee et al. 2004). The recent report of HIV infection of an HLA-B27-positive canarypox vaccinee who made a robust immunodominant response to the Gag KK10 epitope further suggests that current CD8 + lymphocyte-based vaccine modalities are not going to be effective (Betts et al 2005). "
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    ABSTRACT: The only long-term and cost-effective solution to the human immunodeficiency virus (HIV) epidemic in the developing world is a vaccine that prevents individuals from becoming infected or, once infected, from passing the virus on to others. There is currently little hope for an AIDS vaccine. Conventional attempts to induce protective antibody and CD8(+) lymphocyte responses against HIV and simian immunodeficiency virus (SIV) have failed. The enormous diversity of the virus has only recently been appreciated by vaccinologists, and our assays to determine CD8(+) lymphocyte antiviral efficacy are inadequate. The central hypothesis of a CTL-based vaccine is that particularly effective CD8(+) lymphocytes directed against at least five epitopes that are derived from regions under functional and structural constraints will control replication of pathogenic SIV. This would be somewhat analogous to control of virus replication by triple drug therapy or neutralizing antibodies.
    Preview · Article · Apr 2008 · Memórias do Instituto Oswaldo Cruz
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