Maternal antiviral history synergizes with pregnancy and lactation to transfer intergenerational systemic immunity through IgG in milk

  1. Ka Neng Cheong
  2. Juan Sebastian Jara
  3. Leigh M. Sewall
  4. Stanislav Dikiy
  5. Xuan Le
  6. Nicole Wolman
  7. Andrew B. Ward
  8. R. Luke Wiseman
  9. Alejandra Mendoza
Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

Maternal immune transfer is essential for early-life health, yet whether immune experiences before pregnancy shape maternal physiology to optimize immunity in subsequent offspring is unclear. Here, we show that respiratory viral infection before pregnancy confers robust protection against lethal neonatal influenza through antibodies transferred postpartum in milk. Despite the predominance of IgA in milk, antiviral IgG is indispensable for protection. Pregnancy amplifies pre-existing antiviral B cell responses, while prior infection durably reprograms the mammary gland to promote transfer of circulating antiviral IgG into milk. These antibodies retain their epitope specificity, are enriched for broadly protective influenza epitopes, remain functional after passage through the neonatal intestine, and enter offspring circulation through FcRn to provide protection beyond weaning. Natural transmission of virus from infected offspring to mothers establishes maternal immunity that protects future offspring, revealing a coordinated adaptive program that links maternal immune history, pregnancy, and lactation to optimize intergenerational immunity.

Abstract Figure

GRAPHICAL ABSTRACT

HIGHLIGHTS

  • Preconceptual maternal intranasal influenza infection confers complete neonatal B cell mediated protection against lethal neonatal influenza infection that persists beyond weaning into early adulthood.

  • Protection can be transmitted postnatally through milk and is fully dependent on maternal IgG.

  • Pregnancy enhances rather than suppresses antiviral B cell programs in the mother.

  • Milk IgG targets a restricted set of conserved influenza Hemagglutinin epitopes, suggesting selective transfer of broadly protective antibody populations.

  • Protective IgG in milk derives from maternal circulation, not from local B cell mammary gland production.

  • Respiratory infection before pregnancy induces long-lived vascular, stromal, and epithelial transcriptional remodeling of the mammary gland.

  • Neonatal Fc Receptor (FcRn) mediated transport of milk IgG into circulation is required for protection.

  • Infected neonates transmit virus back to mothers, extending protection to subsequent litters for multi-generation protection.

Article activity feed

  1. Version published to 10.64898/2026.08.14.744935 on bioRxiv