Cunningham, Fong, McFarland, Itell, McGuire, Permar, Kumar, Barnett, Borkowsky, Fouda, Gray, Tomaras, Toote, McElrath
In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with a MF59 adjuvanted rgp120 vaccine developed higher magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine if the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59 and Alum adjuvanted HIV envelope vaccines. At peak immunogenicity, the magnitude of gp120 and V1V2-specific IgG responses was comparable between adults and infants immunized with the Alum/MNrg120 vaccine (gp120 median MFI infant: 7,118; adult: 11,510; p=0.070; V1V2 median MFI infant: 512; adult: 804;; p=0.50), whereas infants immunized with the MF59/SF-2 rgp120 vaccine had higher magnitude antibody levels than adults (gp120 median MFI infant: 15,509; adult: 2,290; p<0.001; V1V2 median MFI infant: 23,926; adult: 1538; p<0.001). Six months after peak immunogenicity, infants maintained higher levels Env-specific IgG than adults. Anti-V1V2 IgG3 antibodies that were associated with decreased HIV-1 risk in RV144 vaccinees were present in 43% of MF59/rgp120 vaccinated infants but only in 12% of the vaccinated adults (p=0.0018). Finally, in contrast to rare vaccine-elicited Env-specific IgA in infants, rg120 vaccination elicited Env-specific IgA were frequently detected in adults. Our results suggest that vaccine adjuvants differently modulate gp120-specific antibody responses in adults and infants, and that infants can robustly respond to HIV Env immunization.IMPORTANCE More than 150,000 pediatric HIV infections continue to occur yearly, despite the availability of antiretroviral prophylaxis. A pediatric HIV vaccine could reduce the number of these ongoing infant infections, and also prime for long term immunity prior to sexual debut. We previously reported that immunization of infants with a MF59 adjuvanted recombinant gp120 vaccine induced higher magnitude potentially protective anti-V1V2 IgG responses than in adult vaccinees receiving the moderately effective RV144 vaccine. In the present study, we demonstrate that the robust response observed in infants is not due to differences in vaccine regimen or vaccine dose between adults and infants. Our results suggest that HIV vaccine adjuvants may differentially modulate immune responses in adults and infants, highlighting the need to conduct vaccine trials in pediatric populations.
