Abstract
Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine; but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.
Highlights
The HIV/AIDS epidemic remains a major global health challenge and continues to exert significant strain on healthcare resources in sub-Saharan Africa
The results revealed that the ALVACHIV vaccine significantly primed the neutralizing antibody response of the protein boost and induced cytotoxic T lymphocyte (CTL) activity [59]
The data and safety monitoring board (DSMB) analysed data from 2694 vaccine recipients and 2689 placebo recipients and discovered that 129 HIV infections occurred among the vaccine recipients, and 123 HIV infections occurred among the placebo recipients [91, 92]. These findings indicated that the vaccine was not effective in preventing HIV infection and the DSMB recommended discontinuation of further vaccinations but allowed follow-up to continue
Summary
Despite HIVAC-1e inducing transient and robust T-cell responses, it failed to produce antibodies against HIV infection in other subjects [24, 38] This led researchers to posit that antibody responses could be improved by priming with a recombinant vaccinia vector expressing the HIV-1 envelope and later boosting with an envelope protein. The prime-boost approach, used in several clinical trials, significantly enhanced both humoral and cellular immune responses and induced neutralizing antibodies [24, 53, 54] Despite these promising results, the use of vaccinia virus vectors raised several concerns. In 1999, the Frontiers in Immunology | www.frontiersin.org
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