Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants
Copyright © 2024 Teixeira, Oliveira, Branco, Alberca, Sousa, Leite, Adan, Duarte, Lins, Sato and Viana..
Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 16., Seite 1307546 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Teixeira, Franciane Mouradian Emidio [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 19.02.2024 Date Revised 03.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2024.1307546 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368520285 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368520285 | ||
| 003 | DE-627 | ||
| 005 | 20240403235431.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240216s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2024.1307546 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1363.xml |
| 035 | |a (DE-627)NLM368520285 | ||
| 035 | |a (NLM)38361945 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Teixeira, Franciane Mouradian Emidio |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.02.2024 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Teixeira, Oliveira, Branco, Alberca, Sousa, Leite, Adan, Duarte, Lins, Sato and Viana. | ||
| 520 | |a Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_ΔSTP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_ΔSTP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-ΔSTP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_ΔSTP+Alum protected adult mice upon viral challenge. Collectively, the ZK_ΔSTP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DNA vaccine | |
| 650 | 4 | |a Zika virus | |
| 650 | 4 | |a adjuvants | |
| 650 | 4 | |a envelope protein | |
| 650 | 4 | |a immunogenicity | |
| 650 | 4 | |a membrane-anchoring regions | |
| 650 | 4 | |a protection | |
| 650 | 7 | |a aluminum sulfate |2 NLM | |
| 650 | 7 | |a 34S289N54E |2 NLM | |
| 650 | 7 | |a Vaccines, DNA |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Viral Vaccines |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 650 | 7 | |a Adjuvants, Pharmaceutic |2 NLM | |
| 650 | 7 | |a Alum Compounds |2 NLM | |
| 700 | 1 | |a Oliveira, Luana de Mendonça |e verfasserin |4 aut | |
| 700 | 1 | |a Branco, Anna Cláudia Calvielli Castelo |e verfasserin |4 aut | |
| 700 | 1 | |a Alberca, Ricardo Wesley |e verfasserin |4 aut | |
| 700 | 1 | |a de Sousa, Emanuella Sarmento Alho |e verfasserin |4 aut | |
| 700 | 1 | |a Leite, Bruno Henrique de Sousa |e verfasserin |4 aut | |
| 700 | 1 | |a Adan, Wenny Camilla Dos Santos |e verfasserin |4 aut | |
| 700 | 1 | |a Duarte, Alberto José da Silva |e verfasserin |4 aut | |
| 700 | 1 | |a Lins, Roberto Dias |e verfasserin |4 aut | |
| 700 | 1 | |a Sato, Maria Notomi |e verfasserin |4 aut | |
| 700 | 1 | |a Viana, Isabelle Freire Tabosa |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 15(2024) vom: 16., Seite 1307546 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g day:16 |g pages:1307546 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2024.1307546 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |b 16 |h 1307546 | ||