Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa

Abstract

Objective Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the World Health Organization recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants. Design/Methods We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in 4 African countries. Ninety-three % of HIV+ infants were receiving antiretroviral therapy prior to vaccination. Participants were followed for safety. Immune responses were measured 14 days after three doses of RV5, including serum anti-rotavirus neutralizing and IgA antibodies; IgA antibody in stool; and anti-rotavirus memory B- and T-cell Fluorospot. Shedding of RV5 in stool was monitored. Results 76 HIV+ and 126 HEU infants were enrolled from 2009-2013. No significant differences were found in adverse event rates, including grade 3 events, between RV5 and placebo recipients, for either HIV+ or HEU infants. The proportion of anti-rotavirus IgA responders (≥3-fold increase from baseline) after RV5 administration was 81% in both HIV+ and HEU infants, which was approximately 2.5-fold higher than in placebo recipients (p<0.001). Neutralizing antibody responses to 3 of 5 serotypes were significantly higher after RV5 regardless of HIV status, and those of HIV+ infants were equal or greater than responses of HEU infants to all 5 serotypes. Only one HIV+ RV5 recipient had RV5 isolated from stool. Conclusion RV5 was immunogenic in both HIV+ and HEU infants and no safety signals were observed.

Impfen bei Immundefizienz

“…Generell sollten die Impfungen bei HIV-infizierten Kindern nach den Empfehlungen der STIKO erfolgen und Verzögerungen im Impfschema möglichst vermieden werden. Dies schließt die Rotavirusimpfung von Säuglingen ein [40,41].…”

Inflammation and Immune Activation in Antiretroviral-Treated Human Immunodeficiency Virus Type 1–Infected African Infants and Rotavirus Vaccine Responses

“…Importantly, despite significant differences in inflammation and immune activation at the start of the immunization series in HIV-1+ and HEU African infants, no significant differences in levels achieved in serum neutralizing or IgA antibodies to RV5 were observed [8]. However, negative correlations between pre-vaccination cytokine concentrations and neutralizing antibodies to the surface proteins G1 and P1 (IL-10) and G1 (IFNγ), in the HIV-1+ infants were observed.…”

“…Levels of serum neutralizing antibodies to the surface proteins (G1, G2, G3, G4, and P1 [A]) of the vaccine virus and total serum antirotavirus immunoglobulin A (IgA) to RV5 were determined in the parent trial [8] at baseline and 14 days after the third study dose. Stool antirotavirus IgA antibody (copro-antibody) levels were also measured at baseline and 21 days after each of the 3 study doses [8].…”

“…Stool antirotavirus IgA antibody (copro-antibody) levels were also measured at baseline and 21 days after each of the 3 study doses [8].…”

“…In a randomized, double-blind, placebo-controlled clinical trial (International Maternal Pediatric Adolescent AIDS Clinical Trials [IMPAACT] P1072) of the safety and immunogenicity of RV5 in HIV-1+ and HIV-1-exposed but uninfected (HEU) African infants, plasma concentrations of inflammatory cytokines and soluble CD14 (sCD14) were quantified and correlated with the humoral response to RV5 measured in the parent trial [6].…”