HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine

Abstract

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 an MF59-adjuvanted rgp120 vaccine developed higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine whether 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 magnitudes of the gp120- and V1V2-specific IgG responses were comparable between adults and infants immunized with the alum/MNrgp120 vaccine (gp120 median fluorescence intensities [FIs] in infants = 7,118 and in adults = 11,510, = 0.070; V1V2 median MFIs of 512 [infants] and 804 [adults], = 0.50), whereas infants immunized with the MF59/SF-2 rgp120 vaccine had higher-magnitude antibody levels than adults (gp120 median FIs of 15,509 [infants] and 2,290 [adults], < 0.001; V1V2 median FIs of 23,926 [infants] and 1,538 [adults]; < 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 ( = 0.0018). Finally, in contrast to the rare vaccine-elicited Env-specific IgA in infants, rgp120 vaccine-elicited Env-specific IgA was 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. More than 150,000 pediatric HIV infections 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 an 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.

HIV Env-Specific IgG Antibodies Induced by Vaccination of Neonatal Rhesus Macaques Persist and Can Be Augmented by a Late Booster Immunization in Infancy

“…Our data from the Env-only vaccine regimen are consistent with the induction of persistent Env-specific antibody responses in human infants (10). It should be emphasized again that HIV Env-specific V1V2 IgG responses were induced at a higher magnitude in human infants than in adults (11). Similarly, the hepatitis B vaccine and the human papillomavirus vaccine are known to induce stronger antibody responses in infants than in adults (32,33).…”

“…Highly relevant to the studies here, the retrospective analysis of plasma samples from early HIV Env vaccine trials in human infants demonstrated that vaccination of neonates with HIV Env elicited persistent Env-specific plasma IgG antibodies (10). Furthermore, antibody responses were not only durable for up to 2 years, but the magnitude of plasma IgG antibodies specific to the V1V2 region exceeded those of adults in the RV144 trial (10,11).…”

Simian-Human Immunodeficiency Virus SHIV.CH505-Infected Infant and Adult Rhesus Macaques Exhibit Similar Env-Specific Antibody Kinetics, despite Distinct T-Follicular Helper and Germinal Center B Cell Landscapes

“…Our results suggest that the humoral immune response to SHIV infection develops similarly in adult and infant RMs and corroborate findings in human cohorts demonstrating that infants can develop robust HIV Env binding and neutralizing antibody responses despite their maturing immune landscape. Additionally, we have demonstrated that the Tfh landscape during acute infection in infants is distinct from that in adults, which may offer a potential advantage for infant vaccination, especially since studies suggest that infants are able to mount robust antibody responses to HIV Env vaccination, and these responses tend to be comparable or superior to those of adults (55)(56)(57)(58). However, gaps in our knowledge still exist when it comes to understanding the infant immune response to HIV infection and how it can be harnessed for optimal vaccine-mediated protection against HIV-1.…”

Lessons From COVID-19 in Children: Key Hypotheses to Guide Preventative and Therapeutic Strategies

“…It is known that infants can elicit immune responses of greater breadth compared to adults and develop higher magnitude antibody responses to some protein vaccine antigens like Human Papillomavirus Virus-Like-Particle, HIV, and Hepatitis B. [65][66][67][68][69] Investigating the diversity and potency of pediatric antibody responses may help to define immune correlates of protection against COVID-19 and cross-protective epitopes on S to guide long-term CoV vaccine strategies. candidates expressing viral proteins and immunomodulatory genes (Shenzhen Geno-Immune Medical Institute; Trial IDs: NCT04299724 and NCT04276896).…”