Broad Cross-reactive IgA and IgG Against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection

Abstract

It is currently unclear if SARS-CoV-2 infection or mRNA vaccination can also induce IgG and IgA against common human coronaviruses (HCoVs) in lactating parents. Here we prospectively analyzed human milk (HM) and blood samples from lactating parents to measure the temporal patterns of anti-SARS-CoV-2 specific and anti-HCoV cross-reactive IgA and IgG responses. Two cohorts were analyzed: a vaccination cohort (n=30) who received mRNA-based vaccines for COVID-19 (mRNA-1273 or BNT162b2), and an infection cohort (n=45) with COVID-19 disease. Longitudinal HM and fingerstick blood samples were collected pre- and post-vaccination or, for infected subjects, at 5 time-points 14 - 28 days after confirmed diagnosis. The anti-spike(S) and anti-nucleocapsid(N) IgA and IgG antibody levels against SARS-CoV-2 and HCoVs were measured by multiplex immunoassay (mPlex-CoV). We found that vaccination significantly increased the anti-S IgA and IgG levels in HM. In contrast, while IgG levels increased after a second vaccine dose, blood and HM IgA started to decrease. Moreover, HM and blood anti-S IgG levels were significantly correlated, but anti-S IgA levels were not. SARS2 acute infection elicited anti-S IgG and IgA that showed much higher correlations between HM and blood compared to vaccination. Vaccination and infection were able to significantly increase the broadly cross-reactive IgG recognizing HCoVs in HM and blood than the IgA antibodies in HM and blood. In addition, the broader cross-reactivity of IgG in HM versus blood indicates that COVID-19 vaccination and infection might provide passive immunity through HM for the breastfed infants not only against SARS-CoV-2 but also against common cold coronaviruses.

Vaccines, adjuvants and key factors for mucosal immune response

“…We could suggest that if the natural infection was considered as a nasal prime, the following parenteral vaccine would confer a better immune response. Another study verified that mRNA vaccine increased IgA and IgG in human milk, although IgA decreased earlier than IgG [52].…”

Heterologous SARS‐CoV‐2 IgA neutralising antibody responses in convalescent plasma

“…However, large heterogeneity was observed in the magnitude of the SARS‐CoV‐2 IgA response amongst individuals. Given that IgA is broadly cross‐reactive towards human coronaviruses in milk, saliva and plasma, 32 , 43 , 44 , 45 pre‐existing IgA + memory B cells for human coronaviruses may recognise SARS‐CoV‐2 RBD with higher affinity and undergo somatic hypermutation to create a potent and robust IgA response in some individuals. 46 , 47 Furthermore, cytokine environment and/or host genetics (e.g.…”