Modeling a safer smallpox vaccination regimen, for human immunodeficiency virus type 1-infected patients, in immunocompromised macaques.

Abstract

We have modeled smallpox vaccination with Dryvax (Wyeth) in rhesus macaques that had depletion of CD4(+) T cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. Smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. Unexpectedly, "progressive vaccinia" was infrequent. Vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus NYVAC, before or after retrovirus infection, was safe and lessened the severity of Dryvax-induced skin lesions. Neutralizing antibodies to vaccinia were induced by NYVAC, even in macaques with severe CD4(+) T cell depletion, and their titers inversely correlated with the time to complete resolution of the skin lesions. Together, these results provide the proof of concept, in macaque models that mirror human immunodeficiency virus type 1 infection, that a prime-boost approach with a highly attenuated poxvirus followed by Dryvax increases the safety of smallpox vaccination, and they highlight the importance of neutralizing antibodies in protection against virulent poxvirus.

• Authors: Yvette Edghill-Smith, David Venzon, Tatiana Karpova, James McNally, Janos Nacsa, Wen-Po Tsai, Elzbieta Tryniszewska, Marcin Moniuszko, Jody Manischewitz, Lisa R King, Steven J Snodgrass, John Parrish, Phil Markham, Marsha Sowers, Derrick Martin, Mark G Lewis, Jay A Berzofsky, Igor M Belyakov, Bernard Moss, Jim Tartaglia, Mike Bray, Vanessa Hirsch, Hana Golding, Genoveffa Franchini
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 188 Issue 8 Pg. 1181-91 (Oct 15 2003) ISSN: 0022-1899 [Print] United States
• PMID: 14551889 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Viral
• DryVax vaccine
• NYVAC vaccine
• Smallpox Vaccine
• Vaccines, Attenuated
• Viral Vaccines

Topics

• Animals
• Antibodies, Viral (blood)
• Disease Models, Animal
• HIV Infections (complications)
• HIV-1
• Humans
• Immunization Schedule
• Immunocompromised Host
• Macaca mulatta
• Simian Acquired Immunodeficiency Syndrome (complications)
• Simian Immunodeficiency Virus
• Skin (pathology)
• Smallpox (prevention & control)
• Smallpox Vaccine (administration & dosage, adverse effects, immunology)
• Vaccination
• Vaccines, Attenuated (administration & dosage, adverse effects, immunology)
• Vaccinia virus (immunology)
• Viral Vaccines (administration & dosage, adverse effects, immunology)