HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

Abstract

HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines.

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

“…Other challenges that impact HIV vaccine development include an incomplete understanding of the correlates of immune protection, lack of appropriate animal models, and limited investments by the pharmaceutical industry (19,20). In addition, most traditional immunogen delivery systems are unable to induce potent and long-lasting immunity against HIV and the traditional live attenuated or whole-inactivated virus methods, employed in the design of measles, mumps, and rubella vaccines, are not appropriate for HIV due to legitimate safety and regulatory concerns associated with the risk of permanent integration of proviral HIV DNA into the host genome (4,21).…”

Viral glycoproteomes: technologies for characterization and outlook for vaccine design

“…In addition, such a plethora of protein modifications, combined with mutagenesis due to selection pressure, may complicate the creation of potent and lasting vaccines. Scientific progress is accelerating exponentially, yet prevention and treatment of certain viral infections is lagging behind, notable examples being human immunodeficiency virus type 1 (HIV‐1), herpes simplex viruses (HSV), hepatitis C virus (HCV), and Dengue virus (DENV) . Unpredictable global health challenges, such as recent Ebola virus, Zika virus, and DENV epidemics, urge for preparedness and robust reaction to emerging pathogens .…”

“…HIV‐1 remains among the leading causes of death despite introduction of antiretroviral therapy, especially in sub‐Saharan Africa . Huge resources are, therefore, devoted for development of a vaccine with little success . HIV‐1 envelope glycoprotein precursor gp160 is cleaved into gp120 and membrane bound gp41 that remain noncovalently associated and form a trimer of heterodimers .…”

“…Unfortunately, such vaccination strategies resulted in poor reactivity to gp120 and did not yield neutralization . Although substantial evidence exists regarding native glycosylation of HIV‐1 envelope glycoprotein, few trials have focused on immunization with native trimers .…”

The exceptionally broad-based potential of active and passive vaccination targeting the conserved microbial surface polysaccharide PNAG

“…They were called by the Centers for Disease Control and Infection the most important medical advance of the 20 th century [1], as they are exceedingly successful in preventing infections. Throughout the history of vaccine development, the largest challenge has been the serologic diversity of many, if not most, of the protective antigens, requiring either a large compendium of vaccine components for broad-based coverage ( Streptococcus pneumoniae ) [2], finding a means to deal with a continually evolving target antigen (influenza virus and human immunodeficiency virus) [3,4], or trying to address high in vivo antigenic shifts and drifts ( Plasmodium spp. ) [5].…”