Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120–MF59 in Adults

Abstract

BACKGROUND A safe, effective vaccine is essential to end HIV. A canarypox/protein HIV vaccine regimen showed modest efficacy at reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus demonstrated potent humoral and cellular responses in a Phase 1/2a trial and triggered a Phase 2b/3 double-blinded trial to assess the safety and efficacy of this regimen in South Africa. METHODS We enrolled and randomized 5,404 healthy, HIV-uninfected 18-35-year olds at 14 sites to vaccine (2,704 participants) or placebo (2,700 participants) between 26 October 2016 and 21 June 2019. The vaccine regimen consisted of two ALVAC-HIV (vCP2438) (expressing HIV-1 subtype C env, clade B gp41 , gag and pro) immunizations at months 0 and 1, with booster immunizations of ALVAC-HIV plus bivalent subtype C gp120 protein/MF59 adjuvant at months 3, 6, 12 and 18. Efficacy was evaluated by HIV testing every 3 months. RESULTS In January 2020, pre-specified non-efficacy criteria were met at an interim analysis; further vaccinations were subsequently halted. The vaccines were safe and well-tolerated in the study population (median age 24, 70% female-sex-at-birth). Over the primary 24-month follow-up, there were 133 infections among placebo recipients and 138 among vaccinees (hazard ratio = 1.02; 95%CI, 0.81-1.30; P=0.84). Pre-specified subgroup analyses demonstrated no difference in efficacy by sex or when restricting to follow-up post-4 th vaccination, and no difference amongst female-sex-at-birth by age, BMI, prevalent STIs, behavioral risk score or region. CONCLUSIONS The ALVAC/gp120 regimen did not prevent HIV infection in South Africans despite prior evidence of immunogenicity. ClinicalTrials.gov (NCT02968849)

Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study

“…19 The SEARCH study 20 reported a decrease in HIV incidence of 74% in women who initiated PrEP. Conversely, in the recently completed vaccine trial HVTN 702, 21 PrEP was not provided onsite and few initiated PrEP; HIV incidence was 4•2 per 100 person-years, comparable to ECHO before the introduction of PrEP. 14,21 Our study suggests that the convenience of integrated delivery of PrEP, offered on-site by study staff in the context of a clinical trial, will decrease participants' risk of acquiring HIV.…”

“…Conversely, in the recently completed vaccine trial HVTN 702, 21 PrEP was not provided onsite and few initiated PrEP; HIV incidence was 4•2 per 100 person-years, comparable to ECHO before the introduction of PrEP. 14,21 Our study suggests that the convenience of integrated delivery of PrEP, offered on-site by study staff in the context of a clinical trial, will decrease participants' risk of acquiring HIV. Careful planning, community consultation, and staff training on PrEP initiation are important to attaining high uptake.…”

Cytomegalovirus as an Uninvited Guest in the Response to Vaccines in People Living with HIV

“…This Thai study investigated a vaccine regimen containing the ALVAC-HIV canarypox vector-based vaccine, boosted with a two-component gp120 protein subunit vaccine AIDSVAX ® B/E [ 4 ]. However, the hope faded with the results of the confirmation study HIV Vaccine Trials Network (HVTN) 702 conducted in South Africa using the same prime-boost vaccine regimen on HIV clade C, which was prematurely halted as it met the prespecified stopping criteria for non-efficacy [ 5 ]. The discovery in the sera of PLWH of broadly neutralizing antibodies now provides new clues to design effective vaccine candidates [ 6 , 7 ].…”

Harnessing Natural Mosaics: Antibody-Instructed, Multi-Envelope HIV-1 Vaccine Design

“…Tests of antibody-instructed HIV-1 envelope cocktails have generally been confined to settings of basic research or phase I clinical trials [ 17 , 18 , 19 , 20 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. In past and present years, when HIV-1 research leaders have selected vaccines for advanced clinical trials, they have focused on envelope sequences and clades/subtypes more so than envelope antigenicity [ 11 , 12 , 13 , 14 , 15 , 37 ].…”