Novel prime-boost vaccine strategies against HIV-1

ABSTRACT

Introduction: Given the complexities of HIV infection and the HIV genetic heterogeneity, a successful HIV vaccine should elicit broad adaptive and innate immune responses. Vaccine prime-boost platforms may achieve this goal. Several factors including selection of antigen, type of vector, delivery route, dose, adjuvant, boosting regimen, order of vector injection, and intervals between vaccinations influence the outcome.

Areas covered: We reviewed the literature on the latest findings of the various prime-boost HIV vaccine clinical trials, with particular emphasis on the most advanced and promising strategies.

Expert opinion: Data suggest that heterologous may be better than homologous prime-boost regimens for protection. The most advanced strategies to have reached efficacy trials use either canarypox vector (ALVAC) boosted by adjuvanted gp120 protein or adenovirus (Ad26) vector expressing mosaic antigens boosted by gp140 protein. DNA prime and vectors and/or protein boost regimens are at less advanced development stage. These regimens, while imperfect (efficacy ≥50%), could contribute substantially to the control of HIV epidemics as a part of a comprehensive HIV prevention program. To ensure prompt vaccine access in populations with the greatest need, attention should be given to post-efficacy activities necessary to achieve appropriate uptake and implementation of effective vaccines.

KEYWORDS:

• HIV vaccine
• prime-boost
• viral vector
• ALVAC
• Ad26
• mosaic
• envelope protein
• efficacy
• immune correlates of risk

Article highlights

• It took almost a decade after the results of RV144 to initiate a new efficacy trial based on a similar prime-boost strategy.

• Whether the new vaccine candidate will elicit higher levels of V1V2-binding antibodies and whether these antibodies will be confirmed, as immune correlate of protection remains unknown.

• A mosaic vaccine candidate boosted by an adjuvanted protein is tested for the first time in efficacy trial.

• Although there is a need to increase the number of efficacy trials to test a broad range of vaccines to end the HIV pandemic, a failure of either of these two vaccine strategies may considerably slow the development of an HIV vaccine.

• Although imperfect, regimens conferring partial efficacy would save lives. Modeling studies may provide support to this strategy.

• Post-efficacy roadmap should be developed to ensure expeditious vaccine access in populations with the greatest need.

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.