Infant HIV type 1 gp120 vaccination elicits robust and durable anti-V1V2 immunoglobulin G responses and only rare envelope-specific immunoglobulin A responses

Abstract

Background: Infant responses to vaccines can be impeded by maternal antibodies and immune system immaturity. It is therefore unclear whether human immunodeficiency virus type 1 (HIV-1) vaccination would elicit similar responses in adults and infants.

Method: HIV-1 Env-specific antibody responses were evaluated in 2 completed pediatric vaccine trials. In the Pediatric AIDS Clinical Trials Group (PACTG) 230 protocol, infants were vaccinated with 4 doses of Chiron rgp120 with MF59 (n=48), VaxGen rgp120 with aluminum hydroxide (alum; n=49), or placebo (n=19) between 0 and 20 weeks of age. In PACTG 326, infants received 4 doses of ALVAC-HIV-1/AIDSVAX B/B with alum (n=9) or placebo (n=13) between 0 and 12 weeks of age.

Results: By 52 weeks of age, the majority of maternally acquired antibodies had waned and vaccine Env-specific immunoglobulin G (IgG) responses in vaccinees were higher than in placebo recipients. Chiron vaccine recipients had higher and more-durable IgG responses than VaxGen vaccine recipients or ALVAC/AIDSVAX vaccinees, with vaccine-elicited IgG responses still detectable in 56% of recipients at 2 years of age. Remarkably, at peak immunogenicity, the concentration of anti-V1V2 IgG, a response associated with a reduced risk of HIV-1 acquisition in the RV144 adult vaccine trial, was 22-fold higher in Chiron vaccine recipients, compared with RV144 vaccinees.

Conclusion: As exemplified by the Chiron vaccine regimen, vaccination of infants against HIV-1 can induce robust, durable Env-specific IgG responses, including anti-V1V2 IgG.

Keywords: HIV-1; antibodies; infants; vaccine.

Figure 1.

Human immunodeficiency virus type 1 (HIV-1) Env vaccination induces durable immunoglobulin G (IgG) responses in infants. A, There was no difference in the kinetics of the decline of maternal anti-gp41 IgG antibody level between vaccine and placebo recipients. B, The majority of Chiron vaccine recipients had detectable anti-gp120 IgG responses at week 104 of age, whereas the response rapidly waned in VaxGen vaccine recipients and ALVAC/AIDSVAX recipients. Symbols represent the median IgG response of a vaccine/placebo group. The dashed line represents the positivity cutoff, defined as the mean value + 3 SDs of the mean fluorescence intensity (MFI) of a panel of 60 HIV-1–negative plasma specimens. The number of infant samples available for each vaccine group at each time point is shown on the graph (colors match the legend). Abbreviations: SD, standard deviation; 230, Pediatric AIDS Clinical Trials Group 230; 326, Pediatric AIDS Clinical Trials Group 326.

Figure 2.

Chiron vaccine induces robust human immunodeficiency virus type 1 (HIV-1) Env-specific multiclade immunoglobulin G (IgG) responses. Magnitudes of the IgG responses against multiclade HIV-1 Env gp120 proteins, including the clade B vaccine strains (MN gp120 and GNE8 gp120), a clade C postnatal transmitted/founder Env (4403 BMc5), and a clade AE Env (A244 gp120; RV144 vaccine strain), are presented. The black lines represent median values, and the dashed lines represent the positivity cutoff for each antigen. The Wilcoxon test was used to compare vaccine groups. Abbreviations: MFI, mean fluorescence intensity; 230, Pediatric AIDS Clinical Trials Group 230.

Figure 3.

Human immunodeficiency virus type 1 (HIV-1) Env vaccination elicits high anti-V1V2 immunoglobulin G (IgG) responses in infants. A, Proportions of infants and, for the RV144 vaccine trial, adults with anti-V1V2 IgG responses. ^aData for RV144 vaccinees are from week 26 after vaccination (peak immunogenicity). B, Magnitudes of anti-V1V2 IgG responses in infant recipients of vaccine and placebo. C and D, Correlation between the levels of anti-V1V2 IgG at week 0 of age (maternal) and at week 52 of age (vaccine response) in infant recipients of Chiron (C) and VaxGen (D) vaccines. E, Plasma concentration of CH58 equivalent anti-V1V2 IgG responses in infant recipients of Chiron vaccine and adult recipients of RV144. The Wilcoxon test was used to compare responses between adult and infant vaccinees. Median and 75th percentile values are presented in panel B. Lines in panel E represent median values. Abbreviations: MFI, mean fluorescence intensity; 230, Pediatric AIDS Clinical Trials Group 230; 326, Pediatric AIDS Clinical Trials Group 326.

Figure 4.

Human immunodeficiency virus type 1 (HIV-1) Env vaccination induces anti-V1V2 immunoglobulin G 3 (IgG3) responses in infants. A and B, Frequency (A) and magnitude (B) of anti-V1V2 IgG3 responses in Chiron vaccine recipients. In panel B, the dashed line represents the cutoff, and data points below the cutoff are represented by clear circles. Abbreviations: MFI, mean fluorescence intensity; PACTG 230, Pediatric AIDS Clinical Trials Group 230.