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Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.
Yvette Edghill-Smith1, Mike Bray, Chris A Whitehouse
1Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
The Journal of Infectious Diseases
|January 6, 2005
Summary
Smallpox vaccination is safe but ineffective in protecting immunocompromised macaques against monkeypox if CD4(+) cell counts are low. New vaccination strategies are needed to protect severely immunocompromised individuals.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Helper CD4(+) cells are crucial for adaptive immune responses, including those induced by vaccination.
- Human immunodeficiency virus type 1 (HIV-1) infection severely depletes CD4(+) cells, raising questions about vaccine efficacy in infected individuals.
Purpose of the Study:
- To determine if smallpox vaccination protects human immunodeficiency virus type 1 (HIV-1)-infected individuals.
- To investigate the safety and efficacy of smallpox vaccination in immunodeficient macaques.
Main Methods:
- Immunocompromised macaques were vaccinated with attenuated vaccinia strains.
- Vaccinated macaques were challenged with monkeypox virus.
- Immune responses, including CD4(+) cell counts and immunoglobulin (Ig) switching, were assessed.
Main Results:
- Smallpox vaccination was safe in immunodeficient macaques when preceded by attenuated vaccinia strains.
- Macaques with CD4(+) cell counts <300 cells/mm(3) were not protected against lethal monkeypox virus challenge.
- Lack of protection correlated with a defect in vaccinia-specific IgM to IgG immunoglobulin switching.
Conclusions:
- Smallpox vaccination efficacy is compromised in severely immunocompromised individuals due to impaired CD4(+) cell function.
- Alternative vaccination strategies bypassing CD4(+) cell help are necessary to induce protective IgG responses.
- Developing effective vaccination strategies for immunocompromised populations is critical for infectious disease control.