Antibody responses to prime–boost vaccination with an HIV-1 gp145 envelope protein and chimpanzee adenovirus vectors expressing HIV-1 gp140

Abstract

Objectives Over two million individuals are infected with human immunodeficiency virus type 1 (HIV-1) each year, yet an effective vaccine remains elusive. The most successful HIV-1 vaccine to date demonstrated 31% efficacy. Immune correlate analyses associated HIV-1 envelope (Env)-specific antibodies (Abs) with protection, thus providing a path toward a more effective vaccine. We sought to test the Ab response from novel prime-boost vaccination with a chimpanzee-derived adenovirus (AdC) vector expressing a subtype C Env gp140 combined with either a serologically distinct AdC vector expressing gp140 of a different subtype C isolate or an alum-adjuvanted, partially trimeric gp145 from yet another subtype C isolate. Design Three different prime-boost regimens were tested in mice: AdC prime-protein boost, protein prime-AdC boost, and AdC prime-AdC boost. Each regimen was tested at two different doses of AdC vector in a total of 6 experimental groups. Methods Sera were collected at various timepoints and evaluated by ELISA for Env-specific Ab binding, isotype, and avidity. Ab functionality was assessed by pseudovirus neutralization assay. Results Priming with AdC followed by a protein boost or sequential immunizations with two AdC vectors induced HIV-1 Env-specific binding Abs including those to the V2 region, while priming with protein followed by an AdC boost was relatively ineffective. Abs that cross-neutralized tier 1 HIV-1 from different subtypes were elicited with vaccine regimens that included immunizations with protein. Conclusions Our study warrants further investigation of AdC vector and gp145 protein prime-boost vaccines and their ability to protect against acquisition in animal challenge studies.

Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

“…As in our study protection correlated with titers of binding Abs. It remains to be tested if our regimen, based on sequential use of two SAdV vectors, could be improved further by addition of an Env protein boost, which, as we reported ( Emmer et al, 2016 ), promotes induction of nAbs.…”

“…Sera of RMs were tested for gp160-specific Abs by an ELISA on plates coated with a baculovirus-derived gp160 protein ( Emmer et al, 2016 ).…”

New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission

“…These data strongly support the role of the Ad5 viral vector in enhancing the primary immune response and is the first demonstration of an Ad vector prime, recombinant protein boost strategy for Pfs25, although this has been suggested in the discussion of previous vaccine studies [ 43 ]. The success of this approach shows the promise of a strategy that combines the enhanced T cell activation of an Ad vector priming immunization with boosts using a recombinant protein vaccine [ 21 , 44 ]. Future studies could include the evaluation of the longevity of the response and optimization of the viral vector and dosing schedule.…”

Innovations in HIV-1 Vaccine Design

“…130 To overcome this challenge, researchers shifted to vectors based on other serotypes with lower seroprevalence, such as Ad26 and Ad35, 131 chimeric forms of adenovirus to prevent immune recognition (Ad5H3) using the antigen capsid-incorporation technique, 132 and the chimpanzee-adenovirus vector to which most humans have not been previously exposed. 133 In the antigen capsideincorporation strategy, chimeric Ad5H3 was created by adding a polyhistidine sequence (His 6 ) into the hexon3 (H3) capsid protein of Ad5. The resultant chimeric vector was fit and was not neutralized by Ad5 sera, suggesting its ability to overcome the problem of preexisting immunity.…”