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. 2023 May 4;26(6):106802.
doi: 10.1016/j.isci.2023.106802. eCollection 2023 Jun 16.

Assessment of SARS-CoV-2 neutralizing antibody titers in breastmilk from convalescent and vaccinated mothers

Affiliations

Assessment of SARS-CoV-2 neutralizing antibody titers in breastmilk from convalescent and vaccinated mothers

Christine Bäuerl et al. iScience. .

Abstract

Breastmilk contains antibodies that could protect breastfed infants from infections. In this work, we examined if antibodies in breastmilk could neutralize SARS-CoV-2 in 84 breastmilk samples from women that were either vaccinated (Comirnaty, mRNA-1273, or ChAdOx1), infected with SARS-CoV-2, or both infected and vaccinated. The neutralization capacity of these sera was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. We found that natural infection resulted in higher neutralizing titers and that neutralization correlated positively with levels of immunoglobulin A in breastmilk. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA-based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contains SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.

Keywords: Health sciences; Immune response; Public health; Virology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Frequency distribution of neutralizing antibody titers against Wuhan-Hu-1, Delta, and Omicron BA.1 S variants in breastmilk samples from convalescent mothers (A) Breastmilk samples from mothers infected during March to May 2020 (Wuhan-Hu-1 wave). (B) Breastmilk samples from mothers infected during January to mid-February 2022 (Omicron wave). Fisher’s exact test was used to assess statistical significance. Numbers in the bars indicate the number of samples with detectable NtAb/total number of each group.
Figure 2
Figure 2
Virus-specific-RBD antibody endpoint titers in breastmilk samples from convalescent mothers infected with SARS-CoV-2 during Wuhan-Hu-1 wave and the first Omicron BA.1 wave (A) RBD-IgA Endpoint titer. (B) RBD-IgG Endpoint titer. Mann-Whitney test was used to assess for statistical significance. Box-plots show the median (horizontal line inside box), interquartile range (box), and whiskers depict the minimum and maximum value. Endpoint titers above 1 are considered positive for SARS-CoV-2-specific RBD-IgG and IgA.
Figure 3
Figure 3
ChAdOx1 fails to induce neutralizing antibodies in breastmilk (A) Neutralizing antibody titer (reciprocal IC50) against SARS-CoV-2 ancestral Wuhan-Hu-1 S variant in breastmilk samples of ChAdOx1, mRNA-1273, and Comirnaty-vaccinated lactating mothers at seven days after the second dose. (B) Neutralizing antibody titer (reciprocal IC50) against SARS-CoV-2 ancestral Wuhan-Hu-1 S variant in breastmilk samples of vaccinated lactating mothers compared to convalescent mothers infected during the Wuhan-Hu-1 wave in 2020 (March to May 2020) and during Omicron BA.1 wave (January to mid-February 2022). ∗ Statistical significance to the vaccinated group was calculated with all data from the different vaccine types. Kruskal-Wallis test followed by a Dunn’s multiple comparison test was used to assess for statistical significance. Box-plots show the median (horizontal line inside box), interquartile range (box), and whiskers depict the minimum and maximum value.
Figure 4
Figure 4
NtAb titers against the ancestral SARS-CoV-2 Wuhan-Hu-1 S variant correlate with RBD-specific antibodies in breastmilk from vaccinated mothers Spearman’s correlation analysis between NtAb titers (reciprocal IC50) against the SARS-CoV-2 Wuhan-Hu-1 variant and virus-specific-RBD antibody titers were performed for: (A) RBD-IgA Endpoint titer. (B) RBD-IgG Endpoint titer. Data from different vaccine types were grouped due to the small dataset (n = 16 in each vaccine group: ChAdOx1, mRNA-1273, and Cormirnaty); individual correlations for vaccines are shown in Figure S4.
Figure 5
Figure 5
SARS-CoV-2 infection before vaccination results in higher neutralizing activity against ancestral Wuhan-Hu-1 variant in breastmilk Breastmilk samples from mothers with a past COVID-19 infection and vaccinated with one dose (COVID-19 + D1; n = 5), and mothers vaccinated with two (n = 16) and three doses (n = 10) of Comirnaty vaccine were analyzed for: (A) RBD-IgA Endpoint titer. (B) RBD-IgG Endpoint titer. (C) NtAb titers (reciprocal IC50) against SARS-CoV-2 Wuhan-Hu-1 variant. Kruskal-Wallis test followed by a Dunn’s multiple comparison test was used to assess for statistical significance. Box-plots show the median (horizontal line inside box), interquartile range (box), and whiskers depict the minimum and maximum value. Endpoint titers above 1 are considered positive for SARS-CoV-2-specific RBD-IgG and IgA.

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