SARS-CoV-2 mRNA vaccination in lactating mothers (VLAC) – Characterization of immune responses in serum and breast milk of lactating women

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still poses a serious threat to public health, especially due to the continuous emergence of SARS-CoV-2 variants with particular clinical relevance. Vaccines are considered the most promising strategy for curbing the pandemic. By the end of 2020, several vaccines had become available. Two SARS-CoV-2 mRNA vaccines are registered in Switzerland: Comirnaty® (Pfizer / BioNTech, licensed ≥12 y) and COVID-19 Vaccine Moderna® (licensed ≥18 y). Since early January 2021, the Epidemiology, Biostatistics and Prevention Institute at the University of Zurich serves as the reference vaccine center for the Canton of Zurich and study site of Corona Immunitas with the Zurich SARS-CoV-2 Cohort (ZSAC) and Zurich SARS-CoV-2 Vaccine Cohort (ZVAC) studies. Pregnant and lactating mothers were not included in the initial development and clinical evaluation of COVID-19 vaccines. The FOPH put no restrictions for lactating women on receiving the vaccine. Babies under the age of one year might be at higher risk of severe illness with COVID-19 than older children. This is likely due to their immature immune systems and smaller airways, which make them more likely to develop breathing issues with respiratory virus infections. Infants are currently (02 November 2021) not eligible for vaccination. The first clinical trial studying the Pfizer and BioNTech vaccine in babies aged 6 months started in March 2021.

There is little biological plausibility that the mRNA vaccine will cause harm in infants of breastfeeding women. Testing of the milk of mothers who received either the Pfizer-BioNTech or Moderna vaccine found no mRNA in their milk. The tiny amount of polyethylene glycol-2000 in Pfizer-BioNTech vaccine is not absorbed orally, so breastmilk PEG exposure from maternal immunization is not a concern. Neither of the currently available mRNA vaccines contains a preservative or adjuvant. While there is little plausible risk for the child, there is a biologically plausible benefit. Antibodies stimulated by the vaccine transfer into milk and may protect the breastfeeding child from infection with SARS-CoV-2.

Several studies demonstrated that SARS-CoV-2 specific IgA and IgG antibodies with binding and neutralizing capacity appear in breast milk soon after the first vaccination, with peak levels about 2 weeks after the second vaccine dose. The increase in IgG was higher than the increase in IgA. Breast milk IgG antibodies were synchronized with maternal serum IgG antibodies, and maternal serum antibody titers were equivalent to those of non-breastfeeding women and higher than those of women who previously had COVID-19. Around 7.1% of mothers reported an adverse effect in their breastfed infant, most frequently increased sleepiness and increased fussiness. No serious adverse reaction was reported in infants. A small percentage of women reported a temporary decrease in milk supply after mRNA vaccination or discoloration of milk.

It is essential to study the immunity of lactating women after vaccination, since it is currently unknown whether the antibodies excreted into the breast milk lead to immunization of the child and whether breast milk antibodies also provide protection against novel coronavirus variants. Primary research questions that are currently of high importance are concerned with the neutralizing capacity of vaccine-induced breast milk antibodies against novel variants of concern, the role of IgG in breast milk-transferred immunity, the presence of secretory IgA (sIgA) antibodies in breast milk after vaccination, and the extent of clinical protection from COVID-19 in breastfed infants of vaccinated mothers. Furthermore, T-cell responses specific to the coronavirus and their association with humoral Immune responses, as well as potential differences in T-cell responses between lactating and non-lactating women remain unstudied.

The objectives of our study are the following:

Primary objective:

  • To characterize IgG and IgA antibodies against the trimeric SARS-CoV-2 spike protein in serum and breastmilk: antigen specificity, phenotype and neutralizing capacity produced in response to the mRNA SARS-CoV-2 vaccines over time in lactating women.

Additional objectives:

  • To assess neutralizing antibodies against the trimeric SARS-CoV-2 spike protein of SARS CoV-2 variants in serum and breast milk.
  • To assess the presence and durability of SARS-CoV-2 specific T cell responses over time in serum of lactating women and compare the antibody and T-cell-responses in serum of lactating vs. non-lactating women.
  • To evaluate the occurrence and severity of SARS-CoV-2 infections among lactating women and their infants who received a SARS-CoV-2 vaccine.
  • To evaluate the occurrence and severity of adverse effects among lactating women and their infants who received a SARS-CoV-2 vaccine.
  • To compare the humoral immune response in breast milk between lactating women with SARS-CoV-2 infection and those who received a SARS-COV-2 vaccine.
  • To evaluate factors that influence the immune response in breast milk.
  • To compare the humoral immune response to mRNA SARS-CoV-2 vaccines with the immune responses to the pertussis vaccination in breast milk.