The impact of antigenic distance on Orthopoxvirus Vaccination and Mpox Infection for cross-protective immunity
Abstract Immunological memory mediates rapid protection following infection or vaccination including heterologous exposure. However, cross-reactive memory responses in humans remain poorly characterized. We explored the longevity and specificity of cross-protective responses to orthopoxviruses through smallpox vaccination and Mpox virus (MPXV) infection. Smallpox vaccination using Vaccinia virus (VACV)-based vaccines provides a unique opportunity to study long-term cross-protective immunity without antigen re-exposure. We assessed systemic and mucosal responses in four human cohorts, including first-(Dryvax) and/or third-generation (JYNNEOS) smallpox vaccine recipients (vaccinated 1 week-80 years ago), along with Mpox-infected individuals. First-and third-generation smallpox vaccines elicited strong VACV- and MPXV-specific antibodies. VACV-neutralizing antibodies persisted for decades in first-generation vaccine recipients and were further enhanced after JYNNEOS vaccination. However, despite the high levels of anti-MPXV-specific antibodies in the plasma, cross-neutralization activity was directly correlated with the antigenic distance. Higher neutralization was observed for the cowpox virus (CWPXV) than for MPXV, which showed lower antigenic conservation with VACV. Similarly, Mpox-infected patients had lower neutralization titers for VACV than for CWPXV. Individuals who received vaccination boosters showed more robust, diverse, and prolonged cross-neutralizing responses. Long-term memory analysis revealed an increase in neutralization capacity for VACV over decades, with 80-years-old displaying the most robust humoral response, although this trend was not observed for cross-reactive antigens. Finally, T-cell reactivity to VACV and MPXV epitopes was detected decades post-vaccination, suggesting a role of long-lasting cross-reactive T-cell memory responses in vaccine efficacy. Our findings underscore the pivotal influence of antigenic distance on vaccine effectiveness with implications for cross-protective vaccine design..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 04. Apr. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lucas, Carolina [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.21203/rs.3.rs-3975943/v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XRA042804663 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XRA042804663 | ||
| 003 | DE-627 | ||
| 005 | 20240405131220.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240306s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21203/rs.3.rs-3975943/v1 |2 doi | |
| 035 | |a (DE-627)XRA042804663 | ||
| 035 | |a (ResearchSquare)10.21203/rs.3.rs-3975943/v1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lucas, Carolina |e verfasserin |0 (orcid)0000-0003-4590-2756 |4 aut | |
| 245 | 1 | 0 | |a The impact of antigenic distance on Orthopoxvirus Vaccination and Mpox Infection for cross-protective immunity |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Immunological memory mediates rapid protection following infection or vaccination including heterologous exposure. However, cross-reactive memory responses in humans remain poorly characterized. We explored the longevity and specificity of cross-protective responses to orthopoxviruses through smallpox vaccination and Mpox virus (MPXV) infection. Smallpox vaccination using Vaccinia virus (VACV)-based vaccines provides a unique opportunity to study long-term cross-protective immunity without antigen re-exposure. We assessed systemic and mucosal responses in four human cohorts, including first-(Dryvax) and/or third-generation (JYNNEOS) smallpox vaccine recipients (vaccinated 1 week-80 years ago), along with Mpox-infected individuals. First-and third-generation smallpox vaccines elicited strong VACV- and MPXV-specific antibodies. VACV-neutralizing antibodies persisted for decades in first-generation vaccine recipients and were further enhanced after JYNNEOS vaccination. However, despite the high levels of anti-MPXV-specific antibodies in the plasma, cross-neutralization activity was directly correlated with the antigenic distance. Higher neutralization was observed for the cowpox virus (CWPXV) than for MPXV, which showed lower antigenic conservation with VACV. Similarly, Mpox-infected patients had lower neutralization titers for VACV than for CWPXV. Individuals who received vaccination boosters showed more robust, diverse, and prolonged cross-neutralizing responses. Long-term memory analysis revealed an increase in neutralization capacity for VACV over decades, with 80-years-old displaying the most robust humoral response, although this trend was not observed for cross-reactive antigens. Finally, T-cell reactivity to VACV and MPXV epitopes was detected decades post-vaccination, suggesting a role of long-lasting cross-reactive T-cell memory responses in vaccine efficacy. Our findings underscore the pivotal influence of antigenic distance on vaccine effectiveness with implications for cross-protective vaccine design. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Crandell, Jameson |e verfasserin |4 aut | |
| 700 | 1 | |a Monteiro, Valter |e verfasserin |4 aut | |
| 700 | 1 | |a Pischel, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Zhenhao |e verfasserin |0 (orcid)0000-0002-1246-3665 |4 aut | |
| 700 | 1 | |a Zhong, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Lawres, Lauren |e verfasserin |4 aut | |
| 700 | 1 | |a Conde, Luciana |e verfasserin |4 aut | |
| 700 | 1 | |a Maciel-Silva, Gabriela |e verfasserin |4 aut | |
| 700 | 1 | |a Meira-Assis, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Zaleski, Agnieszka |e verfasserin |4 aut | |
| 700 | 1 | |a Lira, Guilherme |e verfasserin |4 aut | |
| 700 | 1 | |a Higa, Luiza |e verfasserin |4 aut | |
| 700 | 1 | |a Breban, Mallery |e verfasserin |0 (orcid)0000-0002-8976-9988 |4 aut | |
| 700 | 1 | |a Vogels, Chantal |e verfasserin |0 (orcid)0000-0003-0027-6480 |4 aut | |
| 700 | 1 | |a Grubaugh, Nathan |e verfasserin |0 (orcid)0000-0003-2031-1933 |4 aut | |
| 700 | 1 | |a Aoun-Barakat, Lydia |e verfasserin |4 aut | |
| 700 | 1 | |a Grifoni, Alba |e verfasserin |0 (orcid)0000-0002-2209-5966 |4 aut | |
| 700 | 1 | |a Sette, Alessandro |e verfasserin |0 (orcid)0000-0001-7013-2250 |4 aut | |
| 700 | 1 | |a Castiñeiras, Terezinha Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Sidi |e verfasserin |0 (orcid)0000-0002-3819-5005 |4 aut | |
| 700 | 1 | |a Yildirim, Inci |e verfasserin |4 aut | |
| 700 | 1 | |a Vale, André |e verfasserin |4 aut | |
| 700 | 1 | |a Omer, Saad |e verfasserin |0 (orcid)0000-0002-5383-3474 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ResearchSquare.com |g (2024) vom: 04. Apr. |
| 773 | 1 | 8 | |g year:2024 |g day:04 |g month:04 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21203/rs.3.rs-3975943/v1 |m X:VERLAG |x 0 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XRA | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 04 |c 04 | ||