Vaccination or prior infection associated with IgG-dominant response

Vaccination against Covid-19 using an mRNA vaccine was associated with “robust” IgG-predominant response in breast milk in one of the largest studies to date to examine infection and vaccine-induced antibody induction and persistence in human milk.

Covid-19 infection was associated with a highly variable IgA-dominant response in the study, but both infection and mRNA vaccination led to antibodies in breast milk that exhibited neutralizing activity against wild-type SARS-CoV-2.

Writing in the journal JAMA Pediatrics, researcher Kirsi Järvinen, MD, PhD, of the University of Rochester School of Medicine and Dentistry, Rochester, New York, and colleagues wrote that infection resulted “in a relatively universal rapid and long-lasting IgA response, compared with more variable IgG response,” while vaccination resulted in lower initial human milk IgA response with “uniformly larger and more stable” IgG response.

“Human milk showed neutralizing activity in both infection and vaccinated groups with slightly higher activity in the infection group,” they wrote, adding that neutralizing activity was attributed to both IgA and IgG.

“Importantly, whether a dominant IgA or IgG response, both infection and vaccination generated human milk with neutralizing activity. Among other benefits, human milk provides protection against morbidities including respiratory and diarrheal illnesses, owing to specific and non-specific immune factors including antibodies,” the researchers wrote.

They noted that prior to the publication of their study, “to our knowledge, 5 peer-reviewed studies have investigated the human milk antibody response following mRNA vaccination with sample sizes between 5 and 84.”

“These studies show that mRNA vaccination induces specific IgA, IgG and IgM secretion into human milk and generally confirm that, in contrast to Covid-19 illness, human milk response to vaccination is IgG dominant, with IgA appearing approximately 2 weeks after the first dose.”

Järvinen and colleagues conducted a convenience sample analysis involving 47 lactating women with infection, recruited between July and December of 2020, with breast milk samples collected at day 0 (within 14 days of diagnosis), 3, 7, 10, 28 and 90.

The study also included 30 lactating women who received mRNA vaccination against Covid-19 serving as the observational cohort.

In the observational cohort, milk samples were collected pre-vaccination, 18 days after the first dose, and 18 and 90 days after the second dose.

The mean age of the mothers in the main and observational cohort was 29.2 years and 33 years, respectively, and the mean age of their infants was 3.1 months and 7.5 months, respectively.

The analysis showed infection with SARS-CoV-2 to be associated with “a variable human milk IgA and IgG receptor-binding domain–specific antibody response over time that was classified into different temporal patterns: upward trend and level trend (33 of 45 participants [73%]) and low/no response (12 of 45 participants [27%]).”

Infection was also associated with a “robust and quick IgA response” in breast milk that was stable out to 90 days after diagnosis.

The research revealed vaccination to be associated with “a more uniform IgG-dominant response with concentrations increasing after each vaccine dose and beginning to decline by 90 days after the second dose.”

Vaccination was associated with increased breast milk IgA after the first dose only (mean [SD] increase, 31.5 [32.6] antibody units). Breast milk collected after infection and vaccination exhibited microneutralization activity.

Microneutralization activity increased throughout time in the vaccine group only (median [IQR], 2.2 [0] before vaccine vs 10 [4.0] after the first dose; P=0.003) but was higher in the infection group (median [IQR], 20 [67] at day 28) versus the vaccination group after the first-dose human milk samples (P=0.002).

Study limitations included the use of social media to recruit study participants in the infection group, which “pre-selects for participants who have the fiscal and time resources to partake in social media.” Different exclusion criteria were also used for infant age in the two groups, with the infection group limited to infants 6 months of age or younger.

“Additionally, the vaccinated group demographics were narrow, given that the vaccine was only available to health care professionals at the time of recruitment,” the researchers wrote. “This explains the older age and higher education level of the vaccinated group and introduces bias to the study.”

The inclusion of only mRNA vaccine recipients in the study was also cited as a study limitation.

“Our results suggest that 80% of samples exhibit neutralization activity in human milk post-vaccination,” the researchers concluded. “These data are the first to demonstrate this neutralization activity in human milk post-vaccination, to our knowledge.

“…Our findings corroborate (previous data) with wild-type virus assays, showing that 60% of human milk samples exhibit neutralization activity after the first dose and 85% after the second dose. Together, this supports the likelihood of human milk providing infant protection proceeding lactating parental SARS-CoV-2 infection or immunization.”

  1. Covid-19 infection was associated with a highly variable IgA-dominant response in the study, but both infection and mRNA vaccination led to antibodies in breast milk that exhibited neutralizing activity against wild-type SARS-CoV-2.

  2. Human milk showed neutralizing activity in both infection and vaccinated groups with slightly higher activity in the infection group.

Salynn Boyles, Contributing Writer, BreakingMED™

This study was funded by the National Institute of Allergy and Infectious Diseases. Researcher Bridget Young reported receiving grants unrelated to this research from NIDDK. Javinen reported receiving grants from the NIAID and from Janssen outside the submitted work.

Cat ID: 190

Topic ID: 79,190,730,933,190,926,191,41,138,192,927,925,934