The Effectiveness of Anti-COVID-19 Antibodies in Human Milk
by Anne Eglash MD, IBCLC, FABM
There have been several small studies demonstrating the presence of antibodies in human milk after a lactating parent becomes infected with COVID-19 or has been vaccinated with an mRNA vaccine. However, the presence of antibodies does not assume antiviral activity, just as the presence of viral particles does not assume infectivity. One study, for example, identified SARS-CoV-2 virus in breastmilk but the viral particles were, for ease of terms, dead.
The study for this week evaluated the types of antibodies present in human milk after infection among 47 individuals vs 30 who were vaccinated, and whether there was a difference in the antibodies’ ability to inactivate the SARS-CoV-2 virus.
The first day of antibody testing was either approximately 8 days after the last positive COVID-19 test or 18 days after receiving the mRNA vaccine. Not all individuals with natural infection had antibodies in their milk to SARS-CoV-2 virus.
In the infection group that demonstrated antibodies in their milk, 80% and 100% of milk samples demonstrated the ability to neutralize the SARS-CoV-2 virus by day 28 and day 90, respectively. In the vaccine group, 60% and 85% of milk samples neutralized the SARS-CoV-2 virus on day 18 after the first dose, and day 18 after the second dose, respectively.
The authors concluded that both COVID-19 infection and the COVID-19 vaccine induce antibodies in the milk that neutralize the SARS-CoV-2 virus.
What else? See the question!
- Most individuals in the infection group had IgA and IgG antibodies against SARS-CoV-2 virus in their milk when they enrolled in the study, which was on average 8 days after their last positive test.
- Approximately 11% of individuals with natural infection did not have a significant amount of antibodies in their milk.
- Approximately 25% of individuals who were vaccinated did not have a significant amount of antibodies in their milk.
- The infection group were more likely to have predominantly IgA antibodies in their milk by 90 days, whereas the vaccine group were more likely to have predominantly IgG antibodies on their milk. (See the comment about why this is important)
See the Answer
Abstract
Importance
Long-term effect of parental COVID-19 infection vs vaccination on human milk antibody composition and functional activity remains unclear.
Objective
To compare temporal IgA and IgG response in human milk and microneutralization activity against SARS-CoV-2 between lactating parents with infection and vaccinated lactating parents out to 90 days after infection or vaccination.
Design, Setting, and Participants
Convenience sampling observational cohort (recruited July to December 2020) of lactating parents with infection with human milk samples collected at days 0 (within 14 days of diagnosis), 3, 7, 10, 28, and 90. The observational cohort included vaccinated lactating parents with human milk collected prevaccination, 18 days after the first dose, and 18 and 90 days after the second dose.
Exposures
COVID-19 infection diagnosed by polymerase chain reaction within 14 days of consent or receipt of messenger RNA (mRNA) COVID-19 vaccine (BNT162b2 or mRNA-1273).
Main Outcomes and Measures
Human milk anti–SARS-CoV-2 receptor-binding domain IgA and IgG and microneutralization activity against live SARS-CoV-2 virus.
Results
Of 77 individuals, 47 (61.0%) were in the infection group (mean [SD] age, 29.9 [4.4] years), and 30 (39.0%) were in the vaccinated group (mean [SD] age, 33.0 [3.4] years; P = .002). The mean (SD) age of infants in the infection and vaccinated group were 3.1 (2.2) months and 7.5 (5.2) months, respectively (P < .001). Infection was 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 associated with a robust and quick IgA response in human milk that was stable out to 90 days after diagnosis. Vaccination was 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 human milk IgA after the first dose only (mean [SD] increase, 31.5 [32.6] antibody units). Human 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 = .003) but was higher in the infection group (median [IQR], 20 [67] at day 28) vs the vaccination group after the first-dose human milk samples (P = .002). Both IgA and non-IgA (IgG-containing) fractions of human milk from both participants with infection and those who were vaccinated exhibited microneutralization activity against SARS-CoV-2.
Conclusions and Relevance
In this cohort study of a convenience sample of lactating parents, the pattern of IgA and IgG antibodies in human milk differed between COVID-19 infection vs mRNA vaccination out to 90 days. While infection was associated with a highly variable IgA-dominant response and vaccination was associated with an IgG-dominant response, both were associated with having human milk that exhibited neutralization activity against live SARS-CoV-2 virus.
All of the individuals who received the COVID-19 mRNA vaccine developed antibodies to SARS-CoV-2 in their milk, but 11% of those with natural infection did not.
We have so much to learn about how human milk responds to infection, and how the immune response from infection vs vaccine benefits the breastfed/human milk fed infant.
Surprisingly, 11% of individuals who experienced definite COVID-19 infection did not mount adequate antibody response to SARS-CoV-2 in their milk. It would be interesting to know if medication treatment for their infection played a role, such as receiving steroids, which are commonly used for those with COVID-19 pneumonia.
The other fascinating aspect of this study is the difference in milk antibody response between those with infection and those who received the vaccine. Those who experienced infection would be expected to develop IgA antibodies (so no surprise!), since natural infection triggers antibody formation from the gut lining, which is primarily an IgA response. Because vaccines are given by injection and not by mouth, the gut lining does not play a predominant role in forming antibodies, so IgG is the predominant antibody over time.
The big question is which antibodies are most effective for the breastfeeding infant? IgA is considered to be more stable in the acidic environment of the stomach as compared to IgG. Also, IgA naturally hangs out in mucosal surfaces (gut, nose, throat, eustachian tubes, lung) to capture germs that enter the infant’s body, and IgG is not famous for such mucosal activity.
My guess is that the IgA response from natural infection is likely to be more protective for the infant than the IgG response from the vaccine. We have yet to find out!
Vanessa
I wonder, if IgA is more valuable to the infant through naturally acquired passive immunity via breastmilk, would an alternative vaccine route method (ie. Inhalation) be more of a recommended route of administration for mothers than a needle? There was discussion around the use of inhalation vaccines that have been used in the past for Influenza in children. There was discussion around creating this as a next generation vaccine