A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates
As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccine...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/12/2/132 |
| _version_ | 1797296905586212864 |
|---|---|
| author | Sarah N. Tedjakusuma Colin A. Lester Elena D. Neuhaus Emery G. Dora Samanta Gutierrez Molly R. Braun Sean N. Tucker Becca A. Flitter |
| author_facet | Sarah N. Tedjakusuma Colin A. Lester Elena D. Neuhaus Emery G. Dora Samanta Gutierrez Molly R. Braun Sean N. Tucker Becca A. Flitter |
| author_sort | Sarah N. Tedjakusuma |
| collection | DOAJ |
| description | As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge. |
| first_indexed | 2024-03-07T22:11:34Z |
| format | Article |
| id | doaj.art-ecac1522101542b4941be4df1178c00a |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-07T22:11:34Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-ecac1522101542b4941be4df1178c00a2024-02-23T15:36:56ZengMDPI AGVaccines2076-393X2024-01-0112213210.3390/vaccines12020132A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman PrimatesSarah N. Tedjakusuma0Colin A. Lester1Elena D. Neuhaus2Emery G. Dora3Samanta Gutierrez4Molly R. Braun5Sean N. Tucker6Becca A. Flitter7Vaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAVaxart, Inc., South San Francisco, CA 94080, USAAs new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge.https://www.mdpi.com/2076-393X/12/2/132adenovirus vaccinesimmunitymucosalSARS-CoV-2immunoglobulin A |
| spellingShingle | Sarah N. Tedjakusuma Colin A. Lester Elena D. Neuhaus Emery G. Dora Samanta Gutierrez Molly R. Braun Sean N. Tucker Becca A. Flitter A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates Vaccines adenovirus vaccines immunity mucosal SARS-CoV-2 immunoglobulin A |
| title | A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates |
| title_full | A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates |
| title_fullStr | A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates |
| title_full_unstemmed | A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates |
| title_short | A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates |
| title_sort | next generation adenoviral vaccine elicits mucosal and systemic immunogenicity and reduces viral shedding after sars cov 2 challenge in nonhuman primates |
| topic | adenovirus vaccines immunity mucosal SARS-CoV-2 immunoglobulin A |
| url | https://www.mdpi.com/2076-393X/12/2/132 |
| work_keys_str_mv | AT sarahntedjakusuma anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT colinalester anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT elenadneuhaus anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT emerygdora anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT samantagutierrez anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT mollyrbraun anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT seanntucker anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT beccaaflitter anextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT sarahntedjakusuma nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT colinalester nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT elenadneuhaus nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT emerygdora nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT samantagutierrez nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT mollyrbraun nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT seanntucker nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates AT beccaaflitter nextgenerationadenoviralvaccineelicitsmucosalandsystemicimmunogenicityandreducesviralsheddingaftersarscov2challengeinnonhumanprimates |