Long-lasting Immunity from Smallpox Vaccination and Limited Monkeypox Protection

Overview

This study demonstrates that over 80% of individuals vaccinated against smallpox before 1979 retain vaccinia virus antibodies decades later, with partial cross-neutralization against monkeypox virus. However, monkeypox-neutralizing antibody titers are significantly lower, and MVA-BN vaccination boosts immunity but yields limited monkeypox neutralization in vaccine-naïve individuals.

Background

Monkeypox virus (MPXV) has caused a global outbreak since 2022, raising concerns about cross-protection from historic smallpox vaccination. Smallpox vaccination ceased in Taiwan in 1979, leaving younger populations unvaccinated. Orthopoxviruses share antigenic similarities, and historic smallpox vaccines have been estimated to provide approximately 85% protection against mpox. Understanding the durability and cross-neutralizing capacity of antibodies from historic vaccination and the immunogenicity of the MVA-BN vaccine is critical for guiding current prevention strategies.

Data Highlights

Key Findings

• More than 80% of individuals born before 1979 retained vaccinia virus (VACV)-reactive antibodies decades after smallpox vaccination cessation.
• Among VACV-seropositive individuals, 84% exhibited neutralizing activity against VACV.
• Cross-reactive monkeypox virus (MPXV) antibodies were detected in 69% of VACV-seropositive individuals, but only 65% had MPXV-neutralizing capacity.
• MPXV-neutralizing antibody titers were significantly lower than VACV-neutralizing titers, indicating limited cross-protection.
• MVA-BN vaccination boosted both VACV and MPXV antibody levels, but MPXV-neutralizing titers remained low, especially in individuals without prior smallpox vaccination.

Clinical Implications

Historic smallpox vaccination induces durable humoral immunity that provides partial cross-protection against monkeypox virus infection. However, the limited neutralizing capacity against MPXV highlights the need for targeted vaccination strategies, particularly for vaccine-naïve populations. MVA-BN vaccination can enhance orthopoxvirus immunity but may not fully compensate for the lack of prior smallpox immunization in generating robust MPXV-neutralizing antibodies.

Conclusion

Long-lasting antibodies from historic smallpox vaccination confer some degree of cross-protection against monkeypox virus, but neutralizing responses are limited. MVA-BN vaccination boosts immunity but may have restricted effectiveness in MPXV neutralization among those without prior smallpox vaccination.

References

1. World Health Organization/2022 -- Global Mpox Outbreak Data
2. Taiwan Tri-Service General Hospital/2023 -- Serological Analysis of Smallpox and Monkeypox Immunity