Children with perinatally acquired HIV exhibit distinct immune responses to 4CMenB vaccine

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Abstract

Children with perinatally acquired HIV (PHIV) have special vaccination needs, as they make suboptimal immune responses. Here, we evaluated safety and immunogenicity of 2 doses of 4-component group B meningococcal vaccine in antiretroviral therapy–treated children with PHIV and healthy controls (HCs). Assessments included the standard human serum bactericidal antibody (hSBA) assay and measurement of IgG titers against capsular group B Neisseria meningitidis antigens (fHbp, NHBA, NadA). The B cell compartment and vaccine-induced antigen-specific (fHbp+) B cells were investigated by flow cytometry, and gene expression was investigated by multiplexed real-time PCR. A good safety and immunogenicity profile was shown in both groups; however, PHIV demonstrated a reduced immunogenicity compared with HCs. Additionally, PHIV showed a reduced frequency of fHbp+ and an altered B cell subset distribution, with higher fHbp+ frequency in activated memory and tissue-like memory B cells. Gene expression analyses on these cells revealed distinct mechanisms between PHIV and HC seroconverters. Overall, these data suggest that PHIV presents a diverse immune signature following vaccination. The impact of such perturbation on long-term maintenance of vaccine-induced immunity should be further evaluated in vulnerable populations, such as people with PHIV.

Authors

Nicola Cotugno, Alessia Neri, Marco Sanna, Veronica Santilli, Emma Concetta Manno, Giuseppe Rubens Pascucci, Elena Morrocchi, Donato Amodio, Alessandra Ruggiero, Marta Luisa Ciofi degl Atti, Irene Barneschi, Silvia Grappi, Ilaria Cocchi, Vania Giacomet, Daria Trabattoni, Giulio Olivieri, Stefania Bernardi, Daniel O’Connor, Emanuele Montomoli, Andrew J. Pollard, Paolo Palma