Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies
We assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvant...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.910136/full |
| _version_ | 1811291474767118336 |
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| author | Adrian Rice Mohit Verma Emily Voigt Peter Battisti Sam Beaver Sierra Reed Kyle Dinkins Shivani Mody Lise Zakin Shiho Tanaka Brett Morimoto C. Anders Olson Elizabeth Gabitzsch Jeffrey T. Safrit Patricia Spilman Corey Casper Corey Casper Patrick Soon-Shiong |
| author_facet | Adrian Rice Mohit Verma Emily Voigt Peter Battisti Sam Beaver Sierra Reed Kyle Dinkins Shivani Mody Lise Zakin Shiho Tanaka Brett Morimoto C. Anders Olson Elizabeth Gabitzsch Jeffrey T. Safrit Patricia Spilman Corey Casper Corey Casper Patrick Soon-Shiong |
| author_sort | Adrian Rice |
| collection | DOAJ |
| description | We assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvanted S RNA vaccine (AAHI-SC2) delivered by a nanostructured lipid carrier. The AdS+N vaccine encodes S modified with a fusion motif to increase cell-surface expression and an N antigen modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal compartment and increase MHC class I and II stimulation potential. The S sequence in the AAHI-SC2 vaccine comprises the D614G mutation, two prolines to stabilize S in the prefusion conformation, and 3 glutamines in the furin cleavage region to confer protease resistance. CD-1 mice received vaccination by homologous and heterologous prime > boost combinations. Humoral responses to S were the highest with any regimen that included the AAHI-SC2 vaccine, and IgG bound to wild type and Delta (B.1.617.2) variant S1 at similar levels. An AAHI-SC2 prime followed by an AdS+N boost particularly enhanced CD4+ and CD8+ T-cell responses to both wild type and Delta S peptides relative to all other vaccine regimens. Sera from mice receiving AAHI-SC2 homologous or heterologous vaccination were found to be highly neutralizing for all pseudovirus strains tested: Wuhan, Beta, Delta, and Omicron strains. The findings here, taken in consideration with the availability of both vaccines in thermostable formulations, support the testing of heterologous vaccination by an AAHI-SC2 > AdS+N regimen in animal models of SARS-CoV-2 infection to assess its potential to provide increased protection against emerging SARS-CoV-2 variants particularly in regions of the world where the need for cold-chain storage has limited the distribution of other vaccines. |
| first_indexed | 2024-04-13T04:29:56Z |
| format | Article |
| id | doaj.art-dc6ab025ea6648e8bf50a56a033d58df |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T04:29:56Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dc6ab025ea6648e8bf50a56a033d58df2022-12-22T03:02:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.910136910136Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing AntibodiesAdrian Rice0Mohit Verma1Emily Voigt2Peter Battisti3Sam Beaver4Sierra Reed5Kyle Dinkins6Shivani Mody7Lise Zakin8Shiho Tanaka9Brett Morimoto10C. Anders Olson11Elizabeth Gabitzsch12Jeffrey T. Safrit13Patricia Spilman14Corey Casper15Corey Casper16Patrick Soon-Shiong17ImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesAccess to Advanced Health Institute (AAHI), Seattle, WA, United StatesAccess to Advanced Health Institute (AAHI), Seattle, WA, United StatesAccess to Advanced Health Institute (AAHI), Seattle, WA, United StatesAccess to Advanced Health Institute (AAHI), Seattle, WA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesImmunityBio, Inc., Culver City, CA, United StatesAccess to Advanced Health Institute (AAHI), Seattle, WA, United StatesDepartments of Medicine and Global Health, University of Washington, Seattle, WA, United StatesImmunityBio, Inc., Culver City, CA, United StatesWe assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvanted S RNA vaccine (AAHI-SC2) delivered by a nanostructured lipid carrier. The AdS+N vaccine encodes S modified with a fusion motif to increase cell-surface expression and an N antigen modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal compartment and increase MHC class I and II stimulation potential. The S sequence in the AAHI-SC2 vaccine comprises the D614G mutation, two prolines to stabilize S in the prefusion conformation, and 3 glutamines in the furin cleavage region to confer protease resistance. CD-1 mice received vaccination by homologous and heterologous prime > boost combinations. Humoral responses to S were the highest with any regimen that included the AAHI-SC2 vaccine, and IgG bound to wild type and Delta (B.1.617.2) variant S1 at similar levels. An AAHI-SC2 prime followed by an AdS+N boost particularly enhanced CD4+ and CD8+ T-cell responses to both wild type and Delta S peptides relative to all other vaccine regimens. Sera from mice receiving AAHI-SC2 homologous or heterologous vaccination were found to be highly neutralizing for all pseudovirus strains tested: Wuhan, Beta, Delta, and Omicron strains. The findings here, taken in consideration with the availability of both vaccines in thermostable formulations, support the testing of heterologous vaccination by an AAHI-SC2 > AdS+N regimen in animal models of SARS-CoV-2 infection to assess its potential to provide increased protection against emerging SARS-CoV-2 variants particularly in regions of the world where the need for cold-chain storage has limited the distribution of other vaccines.https://www.frontiersin.org/articles/10.3389/fimmu.2022.910136/fullself-amplifying RNADNAvaccinedual antigenheterologousspike |
| spellingShingle | Adrian Rice Mohit Verma Emily Voigt Peter Battisti Sam Beaver Sierra Reed Kyle Dinkins Shivani Mody Lise Zakin Shiho Tanaka Brett Morimoto C. Anders Olson Elizabeth Gabitzsch Jeffrey T. Safrit Patricia Spilman Corey Casper Corey Casper Patrick Soon-Shiong Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies Frontiers in Immunology self-amplifying RNA DNA vaccine dual antigen heterologous spike |
| title | Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies |
| title_full | Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies |
| title_fullStr | Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies |
| title_full_unstemmed | Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies |
| title_short | Heterologous saRNA Prime, DNA Dual-Antigen Boost SARS-CoV-2 Vaccination Elicits Robust Cellular Immunogenicity and Cross-Variant Neutralizing Antibodies |
| title_sort | heterologous sarna prime dna dual antigen boost sars cov 2 vaccination elicits robust cellular immunogenicity and cross variant neutralizing antibodies |
| topic | self-amplifying RNA DNA vaccine dual antigen heterologous spike |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.910136/full |
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