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Published on: May 15, 2014
Third-generation smallpox vaccines induce low-level cross-protecting neutralizing antibodies against Monkeypox virus
Damian Jandrasits1,2,3, Roland Züst1, Denise Siegrist1
1Spiez Laboratory, Federal Office for Civil Protection, Spiez, Switzerland.
Abstract:
Due to the discontinuation of routine smallpox vaccination after its eradication in 1980, a large part of the human population remains naïve against smallpox and other members of the orthopoxvirus genus. As a part of biosafety personnel protection programs, laboratory workers receive prophylactic vaccinations against diverse infectious agents, including smallpox. Here, we studied the levels of cross-protecting neutralizing antibodies as well as total IgG induced by either first- or third-generation smallpox vaccines against Monkeypox virus, using a clinical isolate from the 2022 outbreak. Serum neutralization tests indicated better overall neutralization capacity after vaccination with first-generation smallpox vaccines, compared to an attenuated third-generation vaccine. Results obtained from total IgG ELISA, however, did not show higher induction of orthopoxvirus-specific IgGs in first-generation vaccine recipients. Taken together, our results indicate a lower level of cross-protecting neutralizing antibodies against Monkeypox virus in recipients of third-generation smallpox vaccine compared to first-generation vaccine recipients, although total IgG levels were comparable.
Insights
First-generation smallpox vaccines induce better neutralizing antibodies against monkeypox virus than third-generation vaccines, despite comparable total IgG levels. This finding is crucial for understanding orthopoxvirus cross-protection in a vaccine-naïve population.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Smallpox vaccination ceased in 1980, leaving populations susceptible to orthopoxviruses.
- Laboratory workers may receive smallpox vaccines for occupational safety.
- Monkeypox virus poses a growing public health concern due to cross-reactivity with smallpox immunity.
Purpose of the Study:
- To compare the cross-protective neutralizing antibody and total IgG responses induced by first- and third-generation smallpox vaccines against a clinical isolate of monkeypox virus.
- To assess the efficacy of historical smallpox vaccination in conferring immunity against current orthopoxvirus threats.
Main Methods:
- Serum neutralization tests were performed to evaluate antibody neutralization capacity.
- Enzyme-linked immunosorbent assays (ELISA) were used to quantify total IgG levels.
- A clinical isolate of monkeypox virus from the 2022 outbreak was used for testing.
Main Results:
- First-generation smallpox vaccines demonstrated superior neutralization capacity against monkeypox virus compared to an attenuated third-generation vaccine.
- Total IgG ELISA results did not reveal significantly higher orthopoxvirus-specific IgG induction in first-generation vaccine recipients.
- Recipients of third-generation smallpox vaccines showed lower levels of cross-protecting neutralizing antibodies against monkeypox virus.
Conclusions:
- First-generation smallpox vaccines elicit a more robust neutralizing antibody response against monkeypox virus than third-generation vaccines.
- While total IgG levels may be similar, the quality and breadth of neutralizing antibodies differ between vaccine generations.
- These findings highlight the importance of considering vaccine generation when assessing cross-protection against emergent orthopoxvirus infections.
