Major Scientific Hurdles in HIV Vaccine Development: Historical Perspective and Future Directions

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.

Forty years on: how close is an HIV vaccine?

“…CNS problems, renal and metabolic disorders, and osteoporosis. 2 So, researchers continue their 40-year quest for an HIV vaccine, which could be therapeutic or preventative. Therapeutic vaccination aims to induce or enhance immunity in HIV-positive people to change the disease's trajectory.…”

“…2 They divide group M into nine subtypes, of which A, B and C are the most common. 2,6 Amino acid sequences differ by up to 30% within sub-types and by 42% between subtypes. 2 Between 10% and 20% of HIV-positive people in several parts of Africa are infected with at least two variants.…”

“…2,6 Amino acid sequences differ by up to 30% within sub-types and by 42% between subtypes. 2 Between 10% and 20% of HIV-positive people in several parts of Africa are infected with at least two variants. 2 "In settings where multiple virus subtypes circulate -as in central Africa, for example -mosaic viruses often emerge and spread within the population.…”

“…The nine genes in the HIV genome encode 16 proteins. 2 The proteins on the surface of HIV virions, which are the extracellular viral particles, have a large number of attached carbohydrates (glycosylation). 9 For example, each virion expresses between 7 and 14 'envelope spikes'.…”

“…2 By 1986, the first clinical trial of an HIV vaccine was underway in Zaire (the Democratic Republic of the Congo). 2 Since then, however, more than 250 clinical trials have tested possible HIV vaccines, 2 but none have reached the market.…”