Comparative Profiles of SARS-CoV-2 Spike-Specific Human Milk Antibodies Elicited by mRNA- and Adenovirus-Based COVID-19 Vaccines.

Background: Numerous COVID-19 vaccines are authorized globally. To date, ∼71% of doses comprise the Pfizer/BioNTech vaccine, and ∼17% the Moderna/NIH vaccine, both of which are messenger RNA (mRNA) based. The chimpanzee Ad-based Oxford/AstraZeneca (AZ) vaccine comprises ∼9%, while the Johnson & Johnson/Janssen (J&J) human adenovirus (Ad26) vaccine ranks fourth at ∼2%. No COVID-19 vaccine is yet available for children 0-4. One method to protect this population may be passive immunization through antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work and other reports have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG dominant. Results: In this report, we present a comparative assessment of the milk Ab response elicited by Pfizer, Moderna, J&J, and AZ vaccines. This analysis revealed 86-100% of mRNA vaccine recipient milk exhibited Spike-specific IgG endpoint titers, which were 12- to 28-fold higher than those measured for Ad vaccine recipient milk. Ad-based vaccines elicited Spike-specific milk IgG in only 33-38% of recipients. Specific IgA was measured in 52-71% of mRNA vaccine recipient milk and 17-23% of Ad vaccine recipient milk. J&J recipient milk exhibited significantly lower IgA than Moderna recipients, and AZ recipients exhibited significantly lower IgA titers than Moderna and Pfizer. Less than 50% of milk of any group exhibited specific secretory Ab, with Moderna recipient IgA titers measuring significantly higher than AZ. Moderna appeared to most frequently elicit greater than twofold increases in specific secretory Ab titer relative to prevaccine sample. Conclusion: These data indicate that current Ad-based COVID-19 vaccines poorly elicit Spike-specific Ab in milk compared to mRNA-based vaccines, and that mRNA vaccines are preferred for immunizing the lactating population. This study highlights the need to design vaccines better aimed at eliciting an optimal milk Ab response.