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Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women

Educational Objective
To identify the key insights or developments described in this article
Key Points

Question  What is the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women?

Findings  In this cohort study involving 103 women who received a COVID-19 mRNA vaccine, 30 of whom were pregnant and 16 of whom were lactating, immunogenicity was demonstrated in all, and vaccine-elicited antibodies were found in infant cord blood and breast milk. Pregnant and nonpregnant vaccinated women developed cross-reactive immune responses against SARS-CoV-2 variants of concern.

Meaning  In a small convenience sample, COVID-19 mRNA vaccines were immunogenic in pregnant and lactating women and induced immune responses against SARS-CoV-2 variants.

Abstract

Importance  Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited.

Objective  To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern.

Design, Setting, and Participants  An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection.

Main Outcomes and Measures  SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-γ enzyme-linked immunospot and multiparameter intracellular cytokine–staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants.

Results  This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants.

Conclusion and Relevance  In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.

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Article Information

Corresponding Author: Dan H. Barouch, MD, PhD, Center for Virology and Vaccine Research, 330 Brookline Ave, E/CLS-1043, Boston, MA 02115 (dbarouch@bidmc.harvard.edu).

Accepted for Publication: April 27, 2021.

Published Online: May 13, 2021. doi:10.1001/jama.2021.7563

Author Contributions: Drs Collier and Barouch had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Collier, Alter, Barouch.

Acquisition, analysis, or interpretation of data: Collier, McMahan, Yu, Tostanoski, Aguayo, Ansel, Chandrashekar, Patel, Apraku Bondzie, Sellers, Barrett, Sanborn, Wan, Chang, Anioke, Nkolola, Bradshaw, Jacob-Dolan, Feldman, Gebre, Borducchi, Liu, Schmidt, Suscovich, Linde, Hacker, Barouch.

Drafting of the manuscript: Collier, McMahan, Yu, Chang, Anioke, Barouch.

Critical revision of the manuscript for important intellectual content: Collier, Tostanoski, Aguayo, Ansel, Chandrashekar, Patel, Apraku Bondzie, Sellers, Barrett, Sanborn, Wan, Chang, Nkolola, Bradshaw, Jacob-Dolan, Feldman, Gebre, Borducchi, Liu, Schmidt, Suscovich, Linde, Alter, Hacker, Barouch.

Statistical analysis: Collier, Yu, Tostanoski, Chang, Hacker.

Obtained funding: Schmidt, Barouch.

Administrative, technical, or material support: Collier, McMahan, Yu, Aguayo, Ansel, Chandrashekar, Patel, Apraku Bondzie, Sellers, Barrett, Sanborn, Chang, Anioke, Bradshaw, Feldman, Gebre, Liu, Suscovich, Linde, Barouch.

Supervision: Collier, McMahan, Ansel, Nkolola, Schmidt, Alter, Barouch.

Other - Performing assays: Wan.

Other - methodology, resources, data curation: Alter.

Conflict of Interest Disclosures: Dr Suscovich reported that he is an employee at and owns shares of SeromYx Systems Inc. Dr Linde reported that she is an employee of SeromYx Systems Inc. Dr Alter reported cofounding and serving as a consultant to, and having a patent pending through SeromYx Systems Inc. Dr Barouch reported receiving grants from National Institutes of Health (NIH), the Henry M. Jackson Foundation of the Walter Reed Army Institute of Research, the Bill and Melinda Gates Foundation, the Defense Advanced Research Projects Agency, Gilead, Intima, Alkermes, CureVac, South Africa Medical Research Council, amfAR, Ragon Institute, MassCPR, Sanofi, Legend, and Zentalis; receiving personal fees from SQZ Biotech; and having a patent for COVID-19 vaccines licensed to Janssen with no premarket royalties or payments of any kind. No other disclosures were reported.

Funding/Support: This study was funded by grant CA260476 from the National Institutes of Health (NIH), and grants from the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard, the Massachusetts Consortium for Pathogen Readiness, and the Musk Foundation (DHB); AI146779 from the NIH (AGS); HD000849 from the Reproductive Scientist Development Program from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and from Burroughs Wellcome Fund (AYC), AI007387 from the Multidisciplinary AIDS Training Program (LHT), and TR002541 from the Harvard Clinical and Translational Science Center (MRH).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the participants and their families, the frontline health care providers, and the Center for Virology and Vaccine Research, the Harvard Catalyst Clinical Research Center, the office of the Beth Israel Deaconess Medical Center Chief Academic Officer, and the Department of Obstetrics and Gynecology for enrollment, collection, and processing samples for the Beth Israel Deaconess Medical Center COVID-19 Biorepository.

References
1.
Zambrano  LD , Ellington  S , Strid  P ,  et al; CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team.  Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22-October 3, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-1647. doi:10.15585/mmwr.mm6944e3 PubMedGoogle ScholarCrossref
2.
Rasmussen  SA , Jamieson  DJ .  Pregnancy, postpartum care, and COVID-19 vaccination in 2021.   JAMA. 2021;325(11):1099-1100. doi:10.1001/jama.2021.1683 PubMedGoogle ScholarCrossref
3.
Edlow  AG , Li  JZ , Collier  AY ,  et al.  Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer, and placental pathology in pregnancies during the COVID-19 pandemic.   JAMA Netw Open. 2020;3(12):e2030455. doi:10.1001/jamanetworkopen.2020.30455 PubMedGoogle Scholar
4.
Pace  RM , Williams  JE , Jarvinen  KM ,  et al.  COVID-19 and human milk: SARS-CoV-2, antibodies, and neutralizing capacity.   MedRxiv. Preprint posted online September 18, 2020. doi:10.1101/2020.09.16.20196071Google Scholar
5.
Madhi  SA , Cutland  CL , Kuwanda  L ,  et al; Maternal Flu Trial (Matflu) Team.  Influenza vaccination of pregnant women and protection of their infants.   N Engl J Med. 2014;371(10):918-931. doi:10.1056/NEJMoa1401480 PubMedGoogle ScholarCrossref
6.
Winter  K , Cherry  JD , Harriman  K .  Effectiveness of prenatal tetanus, diphtheria, and acellular pertussis vaccination on pertussis severity in infants.   Clin Infect Dis. 2017;64(1):9-14. doi:10.1093/cid/ciw633 PubMedGoogle ScholarCrossref
7.
Centers for Disease Control and Prevention. Information about COVID-19 vaccines for People who are pregnant or breastfeeding. Accessed March 8, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/pregnancy.html
8.
Gee  J , Marquez  P , Su  J ,  et al.  First month of COVID-19 vaccine safety monitoring—United States, December 14, 2020-January 13, 2021.   MMWR Morb Mortal Wkly Rep. 2021;70(8):283-288. doi:10.15585/mmwr.mm7008e3 PubMedGoogle ScholarCrossref
9.
Baden  LR , El Sahly  HM , Essink  B ,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389 PubMedGoogle ScholarCrossref
10.
Polack  FP , Thomas  SJ , Kitchin  N ,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577 PubMedGoogle ScholarCrossref
11.
Sadoff  J , Le Gars  M , Shukarev  G ,  et al.  Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine.   N Engl J Med. 2021. doi:10.1056/NEJMoa2034201 PubMedGoogle Scholar
12.
Korber  B , Fischer  WM , Gnanakaran  S ,  et al; Sheffield COVID-19 Genomics Group.  Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus.   Cell. 2020;182(4):812-827.e19. doi:10.1016/j.cell.2020.06.043 PubMedGoogle ScholarCrossref
13.
Kemp  SA , Datir  RP , Collier  DA ,  et al.  Recurrent emergence and transmission of a SARS-CoV-2 spike deletion ∆H69/V70.   bioRxiv. Preprint posted online December 21, 2020. dio:10.1101/2020.12.14.422555 Google Scholar
14.
Wibmer  CK , Ayres  F , Hermanus  T ,  et al.  SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma.   Nat Med. 2021;27(4):622-625. doi:10.1038/s41591-021-01285-x PubMedGoogle ScholarCrossref
15.
Wu  K , Werner  AP , Koch  M ,  et al.  serum neutralizing activity elicited by mRNA-1273 vaccine.   N Engl J Med. 2021;384(15):1468-1470. doi:10.1056/NEJMc2102179 PubMedGoogle ScholarCrossref
16.
Feldman  J , Bals  J , St Denis  K ,  et al.  Naive human B cells can neutralize SARS-CoV-2 through recognition of its receptor binding domain.   bioRxiv. Preprint posted online February 10, 2021. doi:10.1101/2021.02.02.429458Google Scholar
17.
McMahan  K , Yu  J , Mercado  NB ,  et al.  Correlates of protection against SARS-CoV-2 in rhesus macaques.   Nature. 2021;590(7847):630-634. doi:10.1038/s41586-020-03041-6PubMedGoogle ScholarCrossref
18.
Chandrashekar  A , Liu  J , Martinot  AJ ,  et al.  SARS-CoV-2 infection protects against rechallenge in rhesus macaques.   Science. 2020;369(6505):812-817. doi:10.1126/science.abc4776 PubMedGoogle ScholarCrossref
19.
Yu  J , Tostanoski  LH , Peter  L ,  et al.  DNA vaccine protection against SARS-CoV-2 in rhesus macaques.   Science. 2020;369(6505):806-811. doi:10.1126/science.abc6284 PubMedGoogle ScholarCrossref
20.
Centers for Disease Control and Prevention. SARS-CoV-2 variant of classifications and definitions. Accessed March 8, 2021. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html
21.
Centers for Disease Prevention and Control. v-safe: after vaccination health checker. Accessed March 8, 2021. https://vsafe.cdc.gov/en/
22.
Wang  Z , Schmidt  F , Weisblum  Y ,  et al.  mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.   Nature. 2021;592(7855):616-622. doi:10.1038/s41586-021-03324-6 PubMedGoogle ScholarCrossref
23.
Atyeo  C , Alter  G .  The multifaceted roles of breast milk antibodies.   Cell. 2021;184(6):1486-1499. doi:10.1016/j.cell.2021.02.031 PubMedGoogle ScholarCrossref
24.
Baird  JK , Jensen  SM , Urba  WJ , Fox  BA , Baird  JR .  SARS-CoV-2 antibodies detected in human breast milk post-vaccination.   MedRxiv. Preprint posted online March 2, 2021. doi:10.1101/2021.02.23.21252328Google Scholar
25.
Muik  A , Wallisch  A-K , Sänger  B ,  et al.  Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera.   Science. 2021;371(6534):1152-1153. doi:10.1126/science.abg6105 PubMedGoogle ScholarCrossref
26.
Liu  Y , Liu  J , Xia  H ,  et al.  Neutralizing activity of BNT162b2-elicited serum.   N Engl J Med. 2021;384(15):1466-1468. doi:10.1056/NEJMc2102017 PubMedGoogle ScholarCrossref
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