Scientists have reported that in most cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, mildly infects infants. However, around 10% of infants experienced severe COVID-19 infection who required advanced medical treatments. In rare cases, even asymptomatic infection can result in Multisystem Inflammatory Syndrome in Children (MIS-C), which is a fatal inflammatory condition. COVID-19 positive young children and infants can also actively transmit SARS-CoV-2 to others. Thereby, it is extremely important to protect this group from infection.

Study: The vaccine-elicited immunoglobulin profile in milk after COVID-19 mRNA-based vaccination is IgG-dominant and lacks secretory antibodies. Image Credit: evso / Shutterstock

COVID-19 vaccination has duly started globally since early 2021.  However, none of the approved vaccines or those currently under clinical trials have considered infants or young children. Therefore, in the current scenario, until efficient pediatric COVID-19 vaccines are authorized and/or herd immunity is achieved, the only way to protect this group is passive immunity. In this approach, antibodies (Abs) are provided to infants through breastfeeding by a COVID-19-vaccinated mother or milk donor.

Previous studies have shown that the total immunoglobulin (Ig) content in mature human milk is around 0.6mg/ml. The level of IgG in milk is approximately 2% of total milk Abs. Researchers have found that around 90% of the milk Abs is IgA, and around 8% is IgM, nearly all in secretory form. Mostly, these secretory IgA and IgM are derived from the gut-associated lymphoid tissue (GALT), known as the entero-mammary link. However, B cells are derived from mucosal-associated lymphoid tissue (MALT).

Scientists believe that determination of infection or vaccination elicited secretory Abs in milk is extremely essential, as this class of Abs is highly stable and resistant to enzymatic degradation in the mucosal lining, i.e., infant oral/nasal cavity, airways, and also in the gastrointestinal tract. A prior study, carried out by the same team of researchers, has shown that 88% of milk from recovered donors, 4 to 6 weeks post COVID-19, contained a high level of Spike-specific IgA, which has a strong correlation with a Spike-specific secretory Ab response. They have also reported a lower level of IgG response.

At present, there is a huge gap in research regarding the immune response of human milk to vaccination. A new study published on the medRxiv* preprint server has focused on analyzing the human milk’s immune response to the novel COVID-19 vaccines. This is the first report on vaccine-elicited Abs in the milk samples collected from individuals who have been vaccinated with lipid-encapsulated mRNA-based COVID-19 vaccines, developed by Pfizer/BioNTech and Moderna.

In this study, individuals who were lactating, had no previous history of a suspected or confirmed SARS-CoV-2 infection, and were scheduled to be vaccinated with either the Pfizer or Moderna’s COVID-19 vaccine were considered. Ten pairs of milk samples were obtained on specific days, i.e., a day before dose 1 of the COVID-19 vaccine, and 14 days after dose 2.

The current study revealed that there are no differences in milk Ab titers among the participants receiving either vaccine. However, the number of participants considered in this study was very low and, in the future, more participants should be considered for an in-depth longitudinal analysis of each COVID-19 vaccine. Both the intramuscular (IM) vaccines were found to generate mucosal Ab, which includes Abs in milk. However, it is unclear if IM vaccination inclines to produce secretory Abs, which is the most protective form of immune response in a mucosal environment.

A prior study reported a higher level of SARS-CoV-2-specific secretory IgA in all participants and a presence of a lower level of IgG in fewer participants. The milk Ab profile of all ten samples considered in the currents study revealed IgG-dominant Spike-targeted Ab with significantly high endpoint binding titers (80%). Ab profiling of post-SARS-CoV-2 infection response revealed significantly lower IgA and secretory Ab titers, i.e., 50% IgA titers and 30% secretory Ab titers. Further, IgA and secretory Ab did not show any positive correlation. This result did not conform with the previous report on post-infection, where IgA and secretory Ab were highly positively correlated, showing that IgA was a largely secretory class. Scientists have explained that even though secretory Abs are extremely essential for the milk Ab defense system, non-secretory Abs, particularly in the case of vaccination, are actively associated with the milk Ab defense system. Non-secretory Abs are derived from serum. Secretory Ab is ultimately produced in milk following IM vaccination.

Scientists believe the continuation of this study will provide a vital opening to bridge the huge research gap regarding the immune response of human milk to vaccination. More research with larger sample sizes is required to draw more information as to which particular COVID-19 vaccine would elicit the best milk Ab response. This research will also emphasize the importance of passive immunity and the necessity to design more effective vaccines to protect breastfeeding infants.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.