Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection
Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed comp...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/9/7/793 |
| _version_ | 1797525955766386688 |
|---|---|
| author | Ying Huang Monique S. França James D. Allen Hua Shi Ted M. Ross |
| author_facet | Ying Huang Monique S. França James D. Allen Hua Shi Ted M. Ross |
| author_sort | Ying Huang |
| collection | DOAJ |
| description | Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection. |
| first_indexed | 2024-03-10T09:21:19Z |
| format | Article |
| id | doaj.art-fb05e2c10d7c43408c71dc37141d0074 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T09:21:19Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-fb05e2c10d7c43408c71dc37141d00742023-11-22T05:13:09ZengMDPI AGVaccines2076-393X2021-07-019779310.3390/vaccines9070793Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus InfectionYing Huang0Monique S. França1James D. Allen2Hua Shi3Ted M. Ross4Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USAPoultry Diagnostic and Research Center, Department of Population Health, University of Georgia, Athens, GA 30602, USACenter for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USACenter for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USACenter for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USAVaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.https://www.mdpi.com/2076-393X/9/7/793influenza virusH1N1 virusvaccinationprotectionimmune responsesmice |
| spellingShingle | Ying Huang Monique S. França James D. Allen Hua Shi Ted M. Ross Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection Vaccines influenza virus H1N1 virus vaccination protection immune responses mice |
| title | Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection |
| title_full | Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection |
| title_fullStr | Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection |
| title_full_unstemmed | Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection |
| title_short | Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection |
| title_sort | next generation of computationally optimized broadly reactive ha vaccines elicited cross reactive immune responses and provided protection against h1n1 virus infection |
| topic | influenza virus H1N1 virus vaccination protection immune responses mice |
| url | https://www.mdpi.com/2076-393X/9/7/793 |
| work_keys_str_mv | AT yinghuang nextgenerationofcomputationallyoptimizedbroadlyreactivehavaccineselicitedcrossreactiveimmuneresponsesandprovidedprotectionagainsth1n1virusinfection AT moniquesfranca nextgenerationofcomputationallyoptimizedbroadlyreactivehavaccineselicitedcrossreactiveimmuneresponsesandprovidedprotectionagainsth1n1virusinfection AT jamesdallen nextgenerationofcomputationallyoptimizedbroadlyreactivehavaccineselicitedcrossreactiveimmuneresponsesandprovidedprotectionagainsth1n1virusinfection AT huashi nextgenerationofcomputationallyoptimizedbroadlyreactivehavaccineselicitedcrossreactiveimmuneresponsesandprovidedprotectionagainsth1n1virusinfection AT tedmross nextgenerationofcomputationallyoptimizedbroadlyreactivehavaccineselicitedcrossreactiveimmuneresponsesandprovidedprotectionagainsth1n1virusinfection |