Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG

Inactivated, whole cell pertussis (wP) vaccines remain at the frontline in the global fight against the resurgence of whooping cough, especially in low- and middle-income countries. However, the reliance on the intracerebral mouse potency test (ic-MPT or Kendrick assay) as the standard batch release assay is challenging for the production of commercial wP vaccines. The ic-MPT is technically challenging, labor intensive and, arguably, incongruous with modern animal welfare guidelines. Replacing the ic-MPT with a whole cell Bordetella pertussis ELISA, the so-called pertussis serology potency test (PSPT), has shown promise, but has been difficult to implement in practice. In this report, we tested the hypothesis that potent and subpotent wP vaccines have distinct serologic profiles in mice that could be developed as a substitute for the ic-MPT. We first established an accelerated decay (thermal stress) protocol in which wP, in the context of DTwP, was rendered >10-fold less effective than unstressed vaccine when evaluated in a mouse model of B. pertussis lung clearance following intranasal challenge. We then screened immune sera on a limited B. pertussis Tahoma I proteome array and identified >30 antigens whose antibody reactivity profiles increased, decreased or were unchanged as a function of wP potency. Interestingly, virtually all the indicator antigens identified are known virulence factors or reactive with human convalescent sera, thereby establishing a potential link between wP potency and pertussis infection and immunity. These results bode well for the development of a limited B. pertussis antigen array as a stability-indicating surrogate potency assay for the ic-MPT.

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Antibodies in breast milk: Pro‐bodies designed for healthy newborn development

Verhasselt,

Tellier,

Carsetti

et al. 2024

Immunological Reviews

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SummaryThis manuscript sheds light on the impact of maternal breast milk antibodies on infant health. Milk antibodies prepare and protect the newborn against environmental exposure, guide and regulate the offspring's immune system, and promote transgenerational adaptation of the immune system to its environment. While the transfer of IgG across the placenta ceases at birth, milk antibodies are continuously replenished by the maternal immune system. They reflect the mother's real‐time adaptation to the environment to which the infant is exposed. They cover the infant's upper respiratory and digestive mucosa and are perfectly positioned to control responses to environmental antigens and might also reach their circulation. Maternal antibodies in breast milk play a key role in the immune defense of the developing child, with a major impact on infectious disease susceptibility in both HIC and LMIC. They also influence the development of another major health burden in children—allergies. Finally, emerging evidence shows that milk antibodies also actively shape immune development. Much of this is likely to be mediated by their effect on the seeding, composition and function of the microbiota, but not only. Further understanding of the bridge that maternal antibodies provide between the child and its environment should enable the best interventions to promote healthy development.

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Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG

Cited by 3 publications

References 75 publications

When Gold is Tarnished: The Impact of Smoker's Breast Milk on Offspring Growth

When Gold is Tarnished: The Impact of Smoker's Breast Milk on Offspring Growth

Antibody Profiles Elicited by Potent and Subpotent Whole Cell Pertussis Vaccines in Mice

Antibodies in breast milk: Pro‐bodies designed for healthy newborn development

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