Prospects for a Globally Effective HIV-1 Vaccine

Abstract

A globally effective vaccine strategy must cope with the broad genetic diversity of HIV and contend with multiple transmission modalities. Understanding correlates of protection and the role of diversity in limiting protective vaccines with those correlates is key. RV144 was the first HIV-1 vaccine trial to demonstrate efficacy against HIV-1 infection. A correlates analysis comparing vaccine-induced immune responses in vaccinated-infected and vaccinated-uninfected volunteers suggested that IgG specific for the V1V2 region of gp120 was associated with reduced risk of HIV-1 infection and that plasma Env IgA was directly correlated with infection risk. RV144 and recent non-human primate (NHP) challenge studies suggest that Env is essential and perhaps sufficient to induce protective antibody responses against mucosally acquired HIV-1. Whether RV144 immune correlates can apply to different HIV vaccines, to populations with different modes and intensity of transmission, or to divergent HIV-1 subtypes remains unknown. Newer prime-boost mosaic and conserved sequence immunization strategies aiming at inducing immune responses of greater breadth and depth as well as the development of immunogens inducing broadly neutralizing antibodies should be actively pursued. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand. Although NHP challenge studies may guide vaccine development, human efficacy trials remain key to answer the critical questions leading to the development of a global HIV-1 vaccine for licensure.

Detection and treatment of Fiebig stage I HIV-1 infection in young at-risk women in South Africa: a prospective cohort study

“…2 Improved understanding of the behavioural factors and biological mechanisms underlying increased HIV acquisition risk in young women is important for prevention strategies. 3 Furthermore, because of inherent adverse effects of lifelong therapy, and persistent immune activation, an HIV cure is needed 4–7 Investigation of the earliest immunological and virological events after HIV infection is essential to vaccine and cure research. ART initiation during the earliest stages of acute HIV infection can reduce transmission risk, viral reservoir size, and T-cell activation and, in some individuals, lead to long-term viral remission after withdrawal of treatment.…”

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine

“…Infant vaccine-elicited antibody responses were durable: V1V2-specific IgG was detected more than 18 months after immunization in most infant vaccinees (18). Since the vaccine efficacy of the RV144 vaccine 1 year after the first vaccination was 60% (19), a vaccine eliciting protective responses similar to RV144 in infants could protect 60% of HIV-exposed infants during the first year of life, when breastfeeding takes place. Therefore, if a pediatric vaccine induces higher levels of antibodies than the RV144 vaccine and these antibodies are present for a longer duration, the efficacy of the pediatric vaccine might be even greater than 60%.…”

Infection of rhesus macaques with a pool of simian immunodeficiency virus with the envelope genes from acute HIV-1 infections

“…However, lack of diverse SHIVenv strains as challenge virus in macaques limits these vaccine and microbicide tests. Several vaccines tested with monovalent challenge SHIV did show complete efficacy in macaques but were less than optimal in human prevention trials [54]. …”