Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines...
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Cold Spring Harbor Laboratory Press
26.08.2021
Cold Spring Harbor Laboratory |
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| Abstract | Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens. |
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| AbstractList | Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens.Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens. Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens. Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike) or modified (mRNA-1273.351, designed for B.1.351 spike) preclinical Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Immunization with high or low dose formulations of mRNA vaccines induced neutralizing antibodies in serum against ancestral SARS-CoV-2 and several variants, although levels were lower particularly against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. Nonetheless, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, and serve as a possible model for waning immunity, showed breakthrough lung infection and pneumonia with B.1.617.2. Thus, as levels of immunity induced by mRNA vaccines decline, breakthrough infection and disease likely will occur with some SARS-CoV-2 variants, suggesting a need for additional booster regimens. Competing Interest Statement M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Kaleido, Moderna, and Emergent BioSolutions. A.C., S.E., and D.K.E. are employees of and shareholders in Moderna Inc. F.K. is a coinventor on a patent application for serological assays and SARS-CoV-2 vaccines (international application numbers PCT/US2021/31110 and 62/994,252). |
| Author | Krammer, Florian Whitener, Bradley Chen, Rita E Shrihari, Swathi Carreño, Juan Manuel VanBlargan, Laura A Kafai, Natasha M Carfi, Andrea Thackray, Larissa B Wilks, Samuel H Karl, Courtney E Smith, Derek J Elbashir, Sayda Mackin, Samantha Hassan, Ahmed O Liang, Chieh-Yu Edwards, Darin K Diamond, Michael S Ying, Baoling Singh, Gagandeep |
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| DOI | 10.1101/2021.08.25.457693 |
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| Notes | SourceType-Working Papers-1 ObjectType-Working Paper/Pre-Print-1 content type line 50 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 Competing Interest Statement: M.S.D. is a consultant for Inbios, Vir Biotechnology, Fortress Biotech, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Kaleido, Moderna, and Emergent BioSolutions. A.C., S.E., and D.K.E. are employees of and shareholders in Moderna Inc. F.K. is a coinventor on a patent application for serological assays and SARS-CoV-2 vaccines (international application numbers PCT/US2021/31110 and 62/994,252). |
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Barnstable County, Massachusetts, July 2021 publication-title: MMWR Morb Mortal Wkly Rep – year: 2021 ident: 2021.08.25.457693v1.28 article-title: Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence publication-title: medRxiv – volume: 118 year: 2021b ident: 2021.08.25.457693v1.17 article-title: Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2 publication-title: Proc Natl Acad Sci U S A – year: 2021a ident: 2021.08.25.457693v1.7 article-title: In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains publication-title: Nature – year: 2020 ident: 2021.08.25.457693v1.27 article-title: Spike mutation D614G alters SARS-CoV-2 fitness publication-title: Nature – year: 2021b ident: 2021.08.25.457693v1.37 article-title: mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants publication-title: Nature – year: 2021 ident: 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| Snippet | Although mRNA vaccines prevent COVID-19, variants jeopardize their efficacy as immunity wanes. Here, we assessed the immunogenicity and protective activity of... |
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| SubjectTerms | Biotechnology Bronchopulmonary infection COVID-19 Immunization Immunogenicity Lymphocytes T Microbiology mRNA mRNA vaccines Patent applications Severe acute respiratory syndrome coronavirus 2 |
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| Title | Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains |
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