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

Three COVID-19 vaccines are licensed for emergency use in the USA: the Pfizer/BioNTech and Moderna/NIH mRNA-based vaccines, and the Johnson & Johnson (J&J)/Janssen human adenovirus (Ad26) vaccine. These vaccines have immunized [~]160 million people nationwide, comprising [~]53% Pfizer, 39% Moderna, and 8% J&J recipients [1]. Although at varying stages of clinical investigation for use in children, no COVID-19 vaccines are yet available for this population, posing a significant public health concern. One method to protect infants and young children may be passive immunization via antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work [2] and other recent reports [3-5] examining the milk Ab response to mRNA-based COVID-19 vaccination 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. In this report, we present a comparative assessment of the milk Ab response elicited by not only the Pfizer and Moderna vaccines, but importantly, the J&J vaccine as well. This analysis revealed that compared to mRNA vaccine recipients, 49% - 63% fewer J&J vaccine recipient milk samples were positive for Spike-specific IgG, with positive samples exhibiting significantly lower mean IgG titers. J&J recipient milk samples contained significantly less specific IgA than Moderna recipient milk samples, which exhibited significantly greater relative IgA increases compared to both Pfizer and J&J recipients. Absolute and relative vaccine-induced secretory Ab titers were similarly low for all groups, though [~]25% more Moderna recipients exhibited a relative increase compared to Pfizer and J&J recipients. These data indicate that J&J vaccine poorly elicits Spike-specific Ab in milk compared to mRNA-based vaccines and that this vaccine should be considered a last choice for immunizing those intending to elicit a strong Ab response in their milk. These data also suggest that Moderna vaccine elicits a superior, albeit moderate, milk (s)IgA response, and highlight the need to design vaccines with optimal protection of the breastfeeding infant in mind.