Milk antibody response after 3rd COVID-19 vaccine and SARS-CoV-2 infection and implications for infant protection

Golan, Yarden; Ilala, Mikias; Li, Lin; Gay, Caryl; Hunagund, Soumya; Lin, Christine Y.; Cassidy, Arianna G.; Jigmeddagva, Unurzul; Matsui, Yusuke; Ozarslan, Nida; Asiodu, Ifeyinwa V.; Ahituv, Nadav; Flaherman, Valerie J.; Gaw, Stephanie L.; Prahl, Mary

doi:10.1016/j.isci.2023.107767

Cited by 4 publications

(5 citation statements)

References 40 publications

(53 reference statements)

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“…Furthermore, IgG antibodies in breast milk may provide protection for many months after vaccination. These data are in contrast to the study by Golan et al, which reported persistently elevated anti-SARS-CoV-2-spike antibody levels in human milk up to 8 months after vaccination, but found that IgG levels declined more notably than IgA levels [22].…”

Section: Discussioncontrasting

confidence: 99%

“…This is corroborated by previous studies that have shown IgG and IgA responses to SARS-CoV-2 infection [10][11][12] and to mRNA vaccination in both the serum and breast milk of lactating mothers [6,10,[12][13][14][15][16][17][18][19][20][21]. It has also been noted that while natural infection produces a robust IgA response [11][12][13][21][22][23], vaccination produces an IgG-dominant response with a lesser IgA response [11][12][13]19,21]. This is not unexpected, given that infection is mediated by mucosal exposure, eliciting an IgA response, whereas vaccination is administered intramuscularly, inducing a more predominant IgG response.…”

Section: Discussionsupporting

confidence: 87%

“…New studies are also needed to determine how the immune properties in mothers' breast milk translate to protection of breast-fed infants and children, including protection against newly emerging SARS-CoV-2 variants. In limited prior studies, anti-RBD antibodies have been detected in the stool, oral mucosa, and saliva of breastfeeding infants following maternal COVID-19 vaccination [19,21,22,30]. Expanding our knowledge of passive immunity to infants will better enable us to protect this vulnerable infant population.…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Antibody Profiles in Maternal Serum and Breast Milk Following mRNA COVID-19 Vaccination: A Longitudinal Prospective Observational Cohort Study

Hsiao,

DiMaggio,

Perez

et al. 2023

Vaccines

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COVID-19 vaccination during pregnancy protects infants against symptomatic COVID-19. Vaccination of lactating mothers may offer additional protection, but our understanding of immune responses in breast milk is limited. We, therefore, performed a single-center prospective cohort study of lactating mothers who received a COVID-19 mRNA primary vaccine series to evaluate the durability, breadth, and neutralizing capacity of the antibody responses in breast milk. Spike IgG- and IgA-binding antibodies of ancestral SARS-CoV-2 in serum and breast milk were quantified over 9 months using Meso Scale Discovery (MSD) V-PLEX assays, and ancestral titers were compared to four variants of concern (Alpha, Beta, Delta, Gamma) at a single time point. Neutralizing antibodies against ancestral SARS-CoV-2 and Omicron BA.4/5 were compared before and after vaccination using a pseudovirus-neutralization assay. Eleven lactating mothers received either Pfizer BNT162b2 (7/11) or Moderna mRNA-1273 (4/11) vaccine primary series. IgG and IgA titers increased in serum and breast milk following each dose, peaking 1–4 weeks after series completion. Titers remained significantly elevated for 7–9 months, except for in breast milk IgA which returned to baseline within 1 month. Furthermore, binding antibodies against all included variants were detected in breast milk collected 1–3 weeks after series completion. However, while vaccination induced a strong neutralizing response against ancestral SARS-CoV-2 in serum and more modest response in breast milk, it did not induce neutralizing antibodies against Omicron BA.4/5 in either specimen type. This study demonstrates that maternal COVID-19 mRNA vaccination may enhance immune protection for infants through breast milk via increased IgG- and IgA-binding-and-neutralizing antibodies; although, variant-specific boosters may be required to optimize immune protection.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Antibody Profiles in Maternal Serum and Breast Milk Following mRNA COVID-19 Vaccination: A Longitudinal Prospective Observational Cohort Study

Hsiao,

DiMaggio,

Perez

et al. 2023

Vaccines

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“…Notably, in this paper we show a significant increase in SARS-CoV-2 specific IgG within human milk post-booster immunization. Similar observations have been described by other researchers studying the humoral response to COVID-19 vaccines (32)(33)(34)(35). IgG in milk was highly correlated to the increase in IgG present in the plasma post-booster.…”

Section: Discussionsupporting

confidence: 90%

“…We and others have previously shown a significant increase in human milk derived SARS-CoV-2 IgA and IgG levels after initial mRNA COVID-19 vaccination series (20,(22)(23)(24)(25)(26). This increase was subsequently followed by a decline, noted 6 months post-vaccination (11,31,32). Notably, in this paper we show a significant increase in SARS-CoV-2 specific IgG within human milk post-booster immunization.…”

Section: Discussionsupporting

confidence: 67%

COVID-19 booster enhances IgG mediated viral neutralization by human milk in vitro

Valcarce,

Stafford,

Neu

et al. 2024

Front. Nutr.

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BackgroundFacilitated by the inability to vaccinate, and an immature immune system, COVID-19 remains a leading cause of death among children. Vaccinated lactating mothers produce specific SARS-CoV-2 antibodies in their milk, capable of neutralizing the virus in vitro. Our objective for this study is to assess the effect of COVID-19 booster dose on SARS-CoV-2 antibody concentration and viral neutralization in milk, plasma, and infant stool.MethodsThirty-nine mothers and 25 infants were enrolled from December 2020 to May 2022. Milk, maternal plasma, and infants' stool were collected at various time-points up to 12 months following mRNA COVID-19 vaccination. A subgroup of 14 mothers received a booster dose. SARS-CoV-2 antibody levels and their neutralization capacities were assessed.ResultsBooster vaccination led to significantly higher IgG levels within human milk and breastfed infants' stool. In vitro neutralization of VSV-gfp-SARS-CoV-2-S-gp, a laboratory safe SARS-CoV-2 like pseudovirus, improved following the booster, with a 90% increase in plasma neutralization and a 60% increase in milk neutralization. We found that post-booster neutralization by human milk was highly correlated to SARS-CoV-2 IgG level. In support of our correlation result, Protein G column depletion of IgG in milk yielded a significant reduction in viral neutralization (p = 0.04).DiscussionThe substantial increase in neutralizing IgG levels in milk and breastfed infants' stool post-booster, coupled with the decrease in milk neutralization capabilities upon IgG depletion, underscores the efficacy of booster doses in augmenting the immune response against SARS-CoV-2 in human milk.

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The importance of COVID-19 vaccination during lactation

Valverde-Merino,

Gomez-Guzman,

Piquer-Martinez

et al. 2024

Infectious Diseases Now

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Milk antibody response after 3rd COVID-19 vaccine and SARS-CoV-2 infection and implications for infant protection

Cited by 4 publications

References 40 publications

SARS-CoV-2 Antibody Profiles in Maternal Serum and Breast Milk Following mRNA COVID-19 Vaccination: A Longitudinal Prospective Observational Cohort Study

SARS-CoV-2 Antibody Profiles in Maternal Serum and Breast Milk Following mRNA COVID-19 Vaccination: A Longitudinal Prospective Observational Cohort Study

COVID-19 booster enhances IgG mediated viral neutralization by human milk in vitro

The importance of COVID-19 vaccination during lactation

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