Maternal alum-adjuvanted recombinant HIV Env vaccine does not enhance autologous virus neutralization in HIV-infected pregnant women

Abstract

Preventive strategies beyond ART will be required to end the pediatric HIV epidemic. A maternal vaccine capable of boosting neutralizing antibody (nAb) responses against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine administered to infected pregnant women can enhance autologous virus neutralization. Here, we assessed autologous virus nAb responses in maternal plasma samples obtained from AIDS Vaccine Evaluation Group (AVEG) Protocols 104 and 102, historical Phase I safety and immunogenicity trials of recombinant HIV Env subunit vaccines in HIV-infected pregnant women (NCT00001041). AVEG 104 participants were randomized to receive 300 {micro}g Env subunit MN recombinant gp120 with alum adjuvant or alum alone. AVEG 102 participants were randomized to receive 640 {micro}g Env subunit recombinant gp160 or placebo. HIV Env-specific maternal plasma binding and neutralizing responses were characterized before and after vaccination in 15 AVEG 104 (n=10 vaccinee, n=5 placebo) and 2 AVEG 102 (n=1 vaccinee, n=1 placebo) participants. Single genome amplification (SGA) was used to obtain HIV env gene sequences from autologous viruses for pseudovirus production in pre- and post-vaccination plasma of HIV-infected pregnant vaccinees (n=6 gp120, n=1 gp160) and placebo recipients (n=3). We detected an increase in MN gp120-specific IgG binding in the vaccinee group between the first immunization visit and the last visit at delivery (p=0.027, 2-sided Wilcoxon test). However, no difference was observed in the neutralization potency of maternal plasma collected at delivery against autologous viruses isolated from early or late pregnancy. Thus, maternal vaccination with gp120/160 did not boost maternal autologous virus nAb responses. Immunization strategies capable of more potent B cell stimulation will likely be required to effectively boost autologous virus nAb responses in pregnant women and synergize with ART to further reduce infant HIV infections. HighlightsO_LIPrior maternal HIV Env vaccine trial did not assess autologous virus neutralization C_LIO_LICirculating viruses isolated from mothers were tested against autologous plasma C_LIO_LIMaternal vaccination with HIV Env gp120/160 increased MN gp120-specific IgG binding C_LIO_LIMaternal HIV Env vaccine regimen did not boost autologous virus neutralization C_LIO_LIMore potent B cell stimulation will be required to elicit autologous nAb responses C_LI