COVID-19 vaccination of lactating mothers elicits specific IgA antibodies in breast milk

Children

In focused attempts to bring an end to the deadly spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic, two new mRNA vaccines were rolled out after receiving emergency use authorization (EUA) by the US Food and Drugs Administration (FDA).

The mRNA vaccines

Both the BNT162b2 Pfizer/BioNTech and mRNA-1273 Moderna/NIH vaccines were created on a messenger ribonucleic acid (mRNA) platform, where the nucleic acid molecule encodes the immunodominant viral spike antigen. The formulation comprises mRNA-encapsulating lipid nanoparticles (LNPs).

These vaccines are administered as a priming dose followed by a boost dose at 28 and 21 days, respectively. Both induce robust, specific antibody and adaptive T cell responses to the virus.

The immunoglobulin G (IgG) antibody titer after immunization was similar to that in convalescent serum, while adverse reactions were low. The overall efficacy against symptomatic infection was 94% and 95%, respectively.

Vaccination in lactating women

While pregnant and lactating mothers were not included in the clinical trials, they are considered a vulnerable group and have been vaccinated as part of the population-based vaccine rollout. Milk from naturally infected mothers is rich in neutralizing IgA and IgG antibodies against the virus.

The American Academy of Pediatrics estimates that children make up 13% of the total cases of COVID-19, and about 3% of them will need hospitalization. The mortality rate is low, at 0.25%.

Human milk contains multiple antibodies, about 90% being sIgA, with 8% and 2% comprising IgM and IgG. These are essential for regulating and developing the full-fledged immune response in infancy.

Vaccines against many respiratory viruses, such as influenza, polio and pertussis, do induce antigen-specific mucosal antibodies, namely, serum IgA and secretory IgA. This can prevent the entry of the virus through the upper airway.

They are also key to neutralizing the virus, preventing its entry into cells and the establishment of productive infection. This has the potential to protect newborn infants against the disease as well.

A new study, released on the medRxiv* preprint server, examines the presence of SARS-CoV-2-specific IgA in human milk and its association with the protection of breastfed infants against the disease.

Study details

The study included 22 healthcare workers without a history of COVID-19. All were lactating, and 21 provided three samples of milk at specified time points – before vaccination, after the first dose, and after the second dose.

Most of them were white women, in their mid-thirties. Seven and 14 of them received the Moderna and Pfizer vaccine, respectively.

Plasma and milk IgA identified

The study showed that there was a marked increase in IgA in human milk, over the period between the first and second time points, and between the second and third time points. Antibodies were successfully elicited in 85% of vaccine recipients, similar to the 80% of individuals who developed IgA antibodies after natural infection.

IgG in human milk

In vaccine recipients, after the second dose, all human milk samples contained IgG antibodies specific to the virus, with the titer showing an increase between the first and second, and the second and third, time points. In milk, IgA was dominant relative to IgG.

Plasma IgG post-vaccination

Again, specific IgG antibodies to the virus were raised after the first and the second doses, becoming highest at 7-10 days from the second dose. Plasma levels were correlated with breast milk levels.

At all time points, total IgA and total IgG levels in human milk and plasma could not be differentiated.

Both vaccines produced similar results, eliciting IgA and IgG levels in breast milk and plasma by the time of the second dose. IgG levels in plasma were higher at this point after the Pfizer vaccine compared to Moderna. However, this does not necessarily imply the functional or clinical superiority of the former.

What are the implications?

The two mRNA vaccines induce the production of specific IgA and IgG in human milk at markedly higher levels over the period from baseline to after the second dose of vaccine. However, IgA responses are dominant in milk following both vaccination and natural infection.

These results stand in opposition to other recent studies, however.

The peak titers of both IgG and IgA in plasma and human milk are seen 7-10 days from the second dose of the vaccine. These antibodies need to be characterized further for their functional efficacy, including avidity of binding, specificity, and neutralizing ability.

It is intriguing that the highest level of virus-specific IgA in human milk was in one mother who was feeding both her babies at the time. Earlier studies have also shown that the titer of secretory IgA in human milk varies with the duration of breastfeeding. More research will be required to confirm and extend these findings.

The study does indicate that vaccination mediates “the potential transfer of protective antibodies to nursing infants.” This could shape vaccination policy for lactating mothers to protect both the mother and the infant simultaneously.

Further studies are needed to determine the potential therapeutic use of human milk IgA to combat SARS-Cov-2 infections and COVID-19.”

*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.

Journal reference:

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