Current views on the potential for development of a HIV vaccine

ABSTRACT

Introduction: Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic.

Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials.

Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses. The follow-up pox-protein trials, developed to replicate and enhance the polyfunctional antibody responses induced by the RV144 regimen, are already reaching efficacy trials, while a large body of work providing a more complete understanding of the development of broadly neutralizing antibodies is now being translated into immunogen design using several different strategies. T-cell based vaccines, fallen out of favor after Ad5-based trials showed increased infection rates in Ad5 seropositive vaccine recipients, are experiencing a comeback based in part on the promising results from non-human primate challenge studies using rhCMV-based immunogens. This diverse array of vaccine candidates may finally allow us to identify a broadly effective HIV vaccine able to contain the epidemic.

KEYWORDS:

• HIV vaccine
• broadly neutralizing antibodies
• efficacy trial
• T-cell based vaccine
• polyfunctional antibodies

Article highlights

• The identification of immune correlates of risk in RV144 precipitated a flurry of new vaccine trial development within the framework of the P5 (Pox-Protein Public Private Partnership)

• Several P5 Phase 1 trials have shown promising results, and a new efficacy trial testing the ALVAC/protein combination optimized for Southern Africa has begun enrollment.

• Heterologous prime-boost concepts that have shown promise in NHP models are also moving into efficacy testing

• Characterization of a vast array of new broad and potent neutralizing antibodies and their maturation pathways in HIV-infected subjects has informed the design of novel immunogens to engage the naïve B-cell repertoire in vaccines for the induction of bnAbs

• Several complementary concepts aimed at inducing cellular immune responses are in, or about to enter, clinical trials

This box summarizes key points contained in the article.

Acknowledgement

The authors thank S Voght of the Fred Hutchinson Cancer Research Center for his critical review of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors are supported by National Institutes of Health and National Institute of Allergy and Infectious Diseases grant UM1AI068618.