COVID-19 vaccine response in pregnant and lactating women: a cohort study

Kathryn J. Gray; Evan A. Bordt; Caroline Atyeo; Elizabeth Deriso; Babatunde Akinwunmi; Nicola Young; Aranxta Medina Baez; Lydia L. Shook; Dana Cvrk; Kaitlyn James; Rose De Guzman; Sara Brigida; Khady Diouf; Ilona Goldfarb; Lisa M. Bebell; Lael M. Yonker; Alessio Fasano; S. Alireza Rabi; Michal A. Elovitz; Galit Alter; Andrea G. Edlow

doi:10.1016/j.ajog.2021.03.023

Original Research: Obstetrics|Articles in Press

COVID-19 vaccine response in pregnant and lactating women: a cohort study

Kathryn J. Gray, MD PhD ^∗
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∗ These authors contributed equally to this work.
Kathryn J. Gray
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∗ These authors contributed equally to this work.
Affiliations
Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical, School, Boston, MA, USA
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Evan A. Bordt, PhD ^∗
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∗ These authors contributed equally to this work.
Evan A. Bordt
Footnotes
∗ These authors contributed equally to this work.
Affiliations
Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Caroline Atyeo, BS ^∗
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∗ These authors contributed equally to this work.
Caroline Atyeo
Footnotes
∗ These authors contributed equally to this work.
Affiliations
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA, USA
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Elizabeth Deriso, PhD
Elizabeth Deriso
Affiliations
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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Babatunde Akinwunmi, MD MPH MMSc
Babatunde Akinwunmi
Affiliations
Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical, School, Boston, MA, USA
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Nicola Young, BA
Nicola Young
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Aranxta Medina Baez, BS
Aranxta Medina Baez
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Lydia L. Shook, MD
Lydia L. Shook
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA, USA
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Dana Cvrk, CNM
Dana Cvrk
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Kaitlyn James, PhD, MPH
Kaitlyn James
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Rose De Guzman, PhD
Rose De Guzman
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Sara Brigida, BA
Sara Brigida
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Khady Diouf, MD
Khady Diouf
Affiliations
Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical, School, Boston, MA, USA
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Ilona Goldfarb, MD MPH
Ilona Goldfarb
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Lisa M. Bebell, MD
Lisa M. Bebell
Affiliations
Division of Infectious Diseases, Massachusetts General Hospital, MGH Center for Global Health, and Harvard Medical School, Boston, MA
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Lael M. Yonker, MD
Lael M. Yonker
Affiliations
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA, USA
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Alessio Fasano, MD
Alessio Fasano
Affiliations
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA, USA
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S. Alireza Rabi, MD
S. Alireza Rabi
Affiliations
Department of Cardiothoracic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Michal A. Elovitz, MD
Michal A. Elovitz
Affiliations
Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Galit Alter, PhD ∗∗
Author Footnotes
∗∗ These authors contributed equally to this work.
Galit Alter
Correspondence
Corresponding Author: Galit Alter. Ragon Institute, Massachusetts General Hospital 400 Technology Square, Cambridge MA 02139 Ph: 857-268-7003 (w, preferred) 617-233-1122 (c)
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∗∗ These authors contributed equally to this work.
Affiliations
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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Andrea G. Edlow, MD, MSc ∗∗
Author Footnotes
∗∗ These authors contributed equally to this work.
Andrea G. Edlow
Correspondence
Corresponding Author: Andrea Edlow. Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114 Ph: 617-724-2229
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∗∗ These authors contributed equally to this work.
Affiliations
Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA, USA
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Author Footnotes
∗ These authors contributed equally to this work.
∗∗ These authors contributed equally to this work.

Open AccessPublished:March 25, 2021DOI:https://doi.org/10.1016/j.ajog.2021.03.023

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Abstract

Background

Pregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking.

Objectives

To evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women compared to: (1) non-pregnant controls and (2) natural COVID-19 infection in pregnancy.

Study Design

131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131) and breastmilk (N=31) at baseline, second vaccine dose, 2-6 weeks post second vaccine, and at delivery by Luminex. Umbilical cord sera (N=10) titers were assessed at delivery. Titers were compared to those of pregnant women 4-12 weeks from natural infection (N=37) by ELISA. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Post-vaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.

Results

Vaccine-induced antibody titers were equivalent in pregnant and lactating compared to non-pregnant women (median [IQR] 5.59 [4.68-5.89] pregnant, 5.74 [5.06-6.22] lactating, 5.62 [4.77-5.98] non-pregnant, p = 0.24). All titers were significantly higher than those induced by SARS-CoV-2 infection during pregnancy (p < 0.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord compared to maternal sera, although this finding did not achieve statistical significance (median [IQR] 104.7 [61.2-188.2] maternal sera, 52.3 [11.7-69.6] cord sera, p=0.05). The second vaccine dose (boost dose) increased SARS-CoV-2-specific IgG, but not IgA, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups.

Conclusions

COVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.

Keywords

Article Info

Publication History

Accepted: March 22, 2021

Received in revised form: March 21, 2021

Received: March 10, 2021

Publication stage

In Press Journal Pre-Proof

Footnotes

DISCLOSURES:

KJG has consulted for Illumina, BillionToOne, and Aetion outsite the submitted work. AF reported serving as a cofounder of and owning stock in Alba Therapeutics and serving on scientific advisory boards for NextCure and Viome outside the submitted work. GA reported serving as a founder of Systems Seromyx. MAE reported serving as medical advisor for Mirvie. All other authors report no conflicts of interest.

SOURCES OF FUNDING:

This work was supported by the National Institutes of Health, including NICHD (grants R01HD100022 and 3R01HD100022-02S20-to AGE), NHLBI (grants K08HL1469630-02 and 3K08HL146963-02S1-to KJG). Additional support was provided by NIAID (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01- to GA; R01A1145840-supplement to MAE), the Gates Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Musk Foundation, the Ragon Institute of MGH and MIT and the Massachusetts General Hospital and Brigham and Women’s Hospital Departments of Obstetrics and Gynecology.

CONDENSATION: COVID-19 vaccination confers a robust humoral response in pregnant and lactating women and immune transfer to neonates via placenta and breastmilk.

AJOG at a GLANCE:

A. Why was this study conducted? Because pregnant and lactating women were excluded from initial COVID-19 vaccine trials, data are lacking regarding vaccine efficacy and infant humoral protection in this population.

B. What are the key findings? Pregnant and lactating women elicited comparable vaccine-induced humoral immune responses to non-pregnant controls, and generated higher antibody titers than those observed following SARS-CoV-2 infection in pregnancy. Vaccine-generated antibodies were present in umbilical cord blood and breastmilk after maternal vaccination.

C. What does this study add to what is already known? This study provides the first data from a large cohort on maternal antibody generation in response to COVID-19 vaccination, compares vaccine-generated immunity to that from natural infection in pregnancy, and suggests vaccination of pregnant and lactating women can confer robust maternal and neonatal immunity.