Evaluation of MRNA-LNP and Adjuvanted Protein SARS-CoV-2 Vaccines in a Maternal Antibody Mouse Model

Overview

Journal NPJ Vaccines

Date 2024 Jun 18

PMID 38890316

Authors

Ross N England

Elizabeth M Drapeau

Mohamad-Gabriel Alameh

Reihaneh Hosseinzadeh

Drew Weissman

Scott E Hensley

Affiliations

Soon will be listed here.

Abstract

Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.

Citing Articles

Immune imprinting: The persisting influence of the first antigenic encounter with rapidly evolving viruses.

Maltseva M, Keeshan A, Cooper C, Langlois M Hum Vaccin Immunother. 2024; 20(1):2384192.

PMID: 39149872 PMC: 11328881. DOI: 10.1080/21645515.2024.2384192.

References

Levy O . Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007; 7(5):379-90. DOI: 10.1038/nri2075. View

Anderson E, Li S, Awofolaju M, Eilola T, Goodwin E, Bolton M . SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared with SARS-CoV-2 mRNA vaccinations. Cell Rep. 2022; 41(3):111496. PMC: 9578169. DOI: 10.1016/j.celrep.2022.111496. View

Amanat F, Stadlbauer D, Strohmeier S, Nguyen T, Chromikova V, McMahon M . A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat Med. 2020; 26(7):1033-1036. PMC: 8183627. DOI: 10.1038/s41591-020-0913-5. View

Flannery D, Gouma S, Dhudasia M, Mukhopadhyay S, Pfeifer M, Woodford E . Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection. JAMA Netw Open. 2022; 5(11):e2240993. PMC: 9647482. DOI: 10.1001/jamanetworkopen.2022.40993. View

Wald E, Schmit K, Gusland D . A Pediatric Infectious Disease Perspective on COVID-19. Clin Infect Dis. 2020; 72(9):1660-1666. PMC: 7454399. DOI: 10.1093/cid/ciaa1095. View

Philbin V, Levy O . Developmental biology of the innate immune response: implications for neonatal and infant vaccine development. Pediatr Res. 2009; 65(5 Pt 2):98R-105R. PMC: 2795575. DOI: 10.1203/PDR.0b013e31819f195d. View

Alameh M, Tombacz I, Bettini E, Lederer K, Sittplangkoon C, Wilmore J . Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses. Immunity. 2021; 54(12):2877-2892.e7. PMC: 8566475. DOI: 10.1016/j.immuni.2021.11.001. View

Niewiesk S . Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol. 2014; 5:446. PMC: 4165321. DOI: 10.3389/fimmu.2014.00446. View

Pardi N, Hogan M, Naradikian M, Parkhouse K, Cain D, Jones L . Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018; 215(6):1571-1588. PMC: 5987916. DOI: 10.1084/jem.20171450. View

10.

Walter E, Talaat K, Sabharwal C, Gurtman A, Lockhart S, Paulsen G . Evaluation of the BNT162b2 Covid-19 Vaccine in Children 5 to 11 Years of Age. N Engl J Med. 2021; 386(1):35-46. PMC: 8609605. DOI: 10.1056/NEJMoa2116298. View

11.

Flannery D, Gouma S, Dhudasia M, Mukhopadhyay S, Pfeifer M, Woodford E . Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios. JAMA Pediatr. 2021; 175(6):594-600. PMC: 7846944. DOI: 10.1001/jamapediatrics.2021.0038. View

12.

Shook L, Atyeo C, Yonker L, Fasano A, Gray K, Alter G . Durability of Anti-Spike Antibodies in Infants After Maternal COVID-19 Vaccination or Natural Infection. JAMA. 2022; 327(11):1087-1089. PMC: 8822441. DOI: 10.1001/jama.2022.1206. View

13.

Willis E, Pardi N, Parkhouse K, Mui B, Tam Y, Weissman D . Nucleoside-modified mRNA vaccination partially overcomes maternal antibody inhibition of de novo immune responses in mice. Sci Transl Med. 2020; 12(525). PMC: 7339908. DOI: 10.1126/scitranslmed.aav5701. View

14.

Polack F, Thomas S, Kitchin N, Absalon J, Gurtman A, Lockhart S . Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020; 383(27):2603-2615. PMC: 7745181. DOI: 10.1056/NEJMoa2034577. View

15.

Rottenstreich A, Zarbiv G, Oiknine-Djian E, Zigron R, Wolf D, Porat S . Efficient Maternofetal Transplacental Transfer of Anti- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Antibodies After Antenatal SARS-CoV-2 BNT162b2 Messenger RNA Vaccination. Clin Infect Dis. 2021; 73(10):1909-1912. PMC: 8083549. DOI: 10.1093/cid/ciab266. View

16.

Fouda G, Martinez D, Swamy G, Permar S . The Impact of IgG transplacental transfer on early life immunity. Immunohorizons. 2018; 2(1):14-25. PMC: 5812294. DOI: 10.4049/immunohorizons.1700057. View

17.

Getahun A, Heyman B . Studies on the mechanism by which antigen-specific IgG suppresses primary antibody responses: evidence for epitope masking and decreased localization of antigen in the spleen. Scand J Immunol. 2009; 70(3):277-87. DOI: 10.1111/j.1365-3083.2009.02298.x. View

18.

Baiersdorfer M, Boros G, Muramatsu H, Mahiny A, Vlatkovic I, Sahin U . A Facile Method for the Removal of dsRNA Contaminant from In Vitro-Transcribed mRNA. Mol Ther Nucleic Acids. 2019; 15:26-35. PMC: 6444222. DOI: 10.1016/j.omtn.2019.02.018. View

19.

Karlsson M, Getahun A, Heyman B . FcgammaRIIB in IgG-mediated suppression of antibody responses: different impact in vivo and in vitro. J Immunol. 2001; 167(10):5558-64. DOI: 10.4049/jimmunol.167.10.5558. View

20.

Hodgins D, Shewen P . Vaccination of neonates: problem and issues. Vaccine. 2011; 30(9):1541-59. DOI: 10.1016/j.vaccine.2011.12.047. View