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A single-dose nanoparticle vaccine protects against mpox in preclinical models
Run-Yu Yuan1, Meng-Jun Li2, Xiao-Bing Lin3
1Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.
Abstract:
The ongoing outbreak and emergence of monkeypox virus (MPXV) clade Ib and IIb lineage have heightened its transmissibility, morbidity, and mortality, underscoring the urgent need for safe and effective vaccines against MPXV infection. In this study, we developed a "two-in-one" nanoparticle vaccine, DAM-NP, which incorporates bivalently fused M1 and A35 antigens conjugated to a self-assembled 24-meric ferritin nanoparticle. Preclinical evaluations demonstrated that DAM-NP elicits robust humoral and cellular immune responses, providing complete protection against lethal vaccinia virus challenge. Importantly, pre-existing antibodies resulting from prior infection with the VACV Tiantan strain utilized for smallpox prevention did not diminish vaccine efficacy. A single dose was sufficient to prevent both morbidity and mortality following a lethal MPXV challenge. These findings establish DAM-NP as a highly immunogenic and promising single-dose vaccine candidate for prevention of MPXV and other orthopoxvirus infections.
Insights
A novel nanoparticle vaccine, DAM-NP, offers complete protection against monkeypox virus (MPXV) and other orthopoxviruses with a single dose. Preclinical studies show it elicits strong immune responses, even with prior vaccinia virus exposure.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- The emergence of monkeypox virus (MPXV) clades Ib and IIb necessitates urgent development of effective vaccines due to increased transmissibility, morbidity, and mortality.
- Existing vaccines may face challenges with pre-existing immunity from vaccinia virus (VACV) infections.
Purpose of the Study:
- To develop and evaluate a novel, single-dose nanoparticle vaccine candidate for MPXV and other orthopoxvirus infections.
- To assess the immunogenicity and protective efficacy of the bivalent vaccine against MPXV challenge.
Main Methods:
- Development of a "two-in-one" nanoparticle vaccine (DAM-NP) by conjugating M1 and A35 antigens to a 24-meric ferritin nanoparticle.
- Preclinical evaluation of DAM-NP in animal models, including assessment of humoral and cellular immune responses.
- Testing vaccine efficacy against lethal vaccinia virus (VACV) and MPXV challenges, considering pre-existing VACV antibodies.
Main Results:
- DAM-NP successfully elicited robust humoral and cellular immune responses in preclinical evaluations.
- The vaccine provided complete protection against lethal VACV challenge.
- A single dose of DAM-NP conferred complete protection against morbidity and mortality following lethal MPXV challenge, irrespective of pre-existing VACV antibodies.
Conclusions:
- DAM-NP is a highly immunogenic and effective single-dose vaccine candidate for MPXV and other orthopoxvirus infections.
- The vaccine's efficacy is not compromised by pre-existing antibodies from VACV Tiantan strain infections.
- These findings support DAM-NP's potential for widespread use in preventing orthopoxvirus outbreaks.
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