We recently demonstrated the ability of an AIDS vaccine consisting of DNA priming and recombinant modified vaccinia Ankara (MVA) booster immunizations (DNA/MVA SHIV vaccine) to control a pathogenic SHIV 89.6P challenge that was administered seven months after the final immunization in macaques (Amara et. al., Science 292, 69-74, 2001). The prototype HIV-1 clade B version of our DNA/MVA vaccine (DNA/MVA HIV vaccine) is entering phase I safety trials in humans in January of 2003. Due to the recent bioterrorism threat the US government is prepared to vaccinate at least a subset of people with the current smallpox vaccine (Dryvax/New York Board of Health strain of vaccinia). The anti-vaccinia virus immunity generated by Dryvax may limit the boosting ability of MVA, hence the efficacy of DNA/MVA HIV vaccines. This is a very important question that needs to be addressed as DNA/MVA vaccines go forward in human trials. There is a serious need for a smallpox vaccine alternative because of the high incidence of adverse events to the current vaccine. Also, many people are not qualified to receive the current smallpox vaccine due to immunodeficiency, skin disorders, old age, young age (< 1 yr), or pregnancy. These groups are major populations and must be accounted for in any reasonable national smallpox vaccination strategy. MVA was developed towards the end of smallpox eradication for use in immunocompromised individuals and was used to vaccinate about 120,000 individuals. However, because smallpox had been controlled in first world countries by the time that MVA was developed, individuals who were vaccinated with MVA were not exposed to variola, and the efficacy of MVA as a smallpox vaccine was not determined. In this proposal we wish to address 1) the effect of preexisting immunity to smallpox on the ability of DNA/MVA vaccine to control pathogenic SHIV challenge, 2) the ability of vaccinia-specific immune responses raised by DNA/MVA vaccine to protect from a lethal monkeypox challenge and 3) the ability of a candidate DNA/MVA vaccine to control both SHIV and monkeypox challenges that are administered sequentially in the presence and absence of preexisting immunity to smallpox.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI057029-05
Application #
7154788
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Pensiero, Michael N
Project Start
2003-07-01
Project End
2008-10-31
Budget Start
2006-11-01
Budget End
2008-10-31
Support Year
5
Fiscal Year
2007
Total Cost
$313,390
Indirect Cost
Name
Emory University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Ganguly, Sumita; Liu, Jinyan; Pillai, Vinod B et al. (2010) Adjuvantive effects of anti-4-1BB agonist Ab and 4-1BBL DNA for a HIV-1 Gag DNA vaccine: different effects on cellular and humoral immunity. Vaccine 28:1300-9
Kannanganat, Sunil; Nigam, Pragati; Velu, Vijayakumar et al. (2010) Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine. J Immunol 185:7262-73
Velu, Vijayakumar; Titanji, Kehmia; Zhu, Baogong et al. (2009) Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature 458:206-10

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