期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 103, 期 -, 页码 186-201出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2022.04.004
关键词
Maternal vaccination; Group B Streptococcus; GAPDH; Microbiome; Neonates; Microglia
资金
- Foundation for Science and Technology (FCT)
- European Regional Development Fund (FEDER)
- Compete [POCI-01-0145-FEDER-016607 (PTDC/IMI-MIC/1049/2014)]
- French Governments Investissement dAvenir programme, Laboratoire dExcellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
- FRM [DBF20160635740]
- FCT [CEECIND/03675/2018, 2020.05394.BD]
- Fundação para a Ciência e a Tecnologia [2020.05394.BD] Funding Source: FCT
This study found that using GBS GAPDH as a maternal vaccine candidate may result in abnormal development of the offspring's intestinal and immune systems, as well as behavioral abnormalities later in life.
Group B Streptococcus (GBS) remains a major neonatal life-threatening pathogen. We initially identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a promising vaccine candidate against GBS. Since GAPDH is highly conserved, we investigate whether GBS GAPDH maternal vaccination interferes with the intestinal colonization of the offspring and the development of its mucosal immune system and central nervous system. An altered gut microbiome with increased Proteobacteria is observed in pups born from vaccinated dams during early life. These pups present decreased relative expression of IL-1 beta, IL-17A, RegIII gamma and MUC2 in the distal colon. They also display increased CD11b, F4/80 and MHC class II expression on microglia in early life and marked reduction of Ly6C+ cells and neutrophils. Importantly, male mice born from vaccinated mothers present behavioral abnormalities during adulthood, including decreased exploratory behavior, a subtle anxious-like phenotype and global alterations in spatial learning and memory strategies, and higher sensitivity to a stressful stimulus. Our study highlights the danger of using ubiquitous antigens in maternal human vaccines against neonatal pathogens.
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