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Children with perinatally acquired HIV exhibit distinct immune responses to 4CMenB vaccine
Nicola Cotugno, … , Andrew J. Pollard, Paolo Palma
Nicola Cotugno, … , Andrew J. Pollard, Paolo Palma
Published May 22, 2024
Citation Information: JCI Insight. 2024;9(10):e177182. https://doi.org/10.1172/jci.insight.177182.
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Research Article AIDS/HIV Vaccines

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

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Figure 1

4CMenB vaccine elicits hSBA response in PHIV and HC participants.

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4CMenB vaccine elicits hSBA response in PHIV and HC participants.
hSBA t...
hSBA titers were measured in the sera of participants at T0, T2, and T3. (A) Study design. (B) Pearsonʼs correlation analyses between baseline hSBA values and age at T0. Regression line is reported in blue (n = 63). (C) Line plot reporting the percentage of participants per hSBA level at T0 (dashed lines) and T2 (solid lines) for HC (n = 25, blue) and PHIV (n = 50, red) groups and early-treated (n = 20, cyan) and late-treated (n = 28, orange) PHIV individuals. Gray dashed line marks the threshold of seroprotection (hSBA T0 = 4), with gray area showing nonseroprotection. (D) Longitudinal analyses of hSBA titer (±95% CI) in HC (n = 19, blue), PHIV (n = 39, red), and early-treated (n = 16, cyan) and late-treated (n = 23, orange) individuals pre- (T0) and postvaccination (T2–T3). The lines represent the median values of HC (blue), PHIV (red), and early-treated (cyan) and late-treated (orange) individuals. (E) Log2 hSBA titer fold-change (FC) (±95% CI) in HC (n = 25, blue), PHIV (n = 50, red), and early-treated (n = 20, cyan) and late-treated (n = 28, orange) participants following vaccination. The size of the points represents the hSBA value at T0. The dashed line represents the threshold of protection (FC ≥ 4); numbers and percentage of seroconverter (SC) and nonseroconverter (NSC) participants are reported for each group. Box plot midlines report the median, with the upper and lower limits of the box being 75th and 25th percentile, respectively. Whiskers represent 1.5 IQR. Comparison of hSBA distributions between groups and time points was evaluated by 2-way ANOVA followed by pairwise t test if both distributions were normal, or conversely, with Kruskal-Wallis test followed by Dunn’s test. FDR-adjusted P values less than 0.05 are reported.

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