Approximately 1 out of every 5 Americans is infected with herpes simplex virus type 2 (HSV-2). Localized genital infection by HSV-2 results in painful recurring genital lesions while disseminated infection can involve multiple visceral organs and lethal encephalitis. Using Phase 1 funding we have developed a new heterologous immunization protocol composed of a glycoprotein D (gD) DNA vaccine followed by a liposome-encapsulated gD boost. This protocol induces robust serum IgG antigen-specific antibodies, mucosal IgG and secretory IgA and a T helper type 1 (Th1)-biased immune response. Mice immunized with this protocol are protected from disease after infection with 100 times the lethal dose of virus. Use of a higher priming dose of DNA revealed sterilizing immunity in 80% of immunized mice. We are requesting Phase 2 funding to complement and extend the studies in preparation for preclinical safety testing. The requested funding will be used to further characterize immune mediators induced by the novel HSV-2 vaccine. Funding will also be used to evaluate commercial suppliers of vaccine components and establish quality control parameters. Dosing of components will be further optimized in preparation for human use and toxicity testing. Guinea pigs will be used to demonstrate efficacy of the vaccine in a second animal model and to test the ability of the vaccine to prevent establishment of latency and/or reactivation of latent virus. The end result of these experiments will be the establishment of a novel vaccine for HSV-2.

Public Health Relevance

This vaccine would clearly have an impact on the greater than $1.6 billion spent annually on direct medical costs associated with HSV-2. The Public Health Service (PHS) has recognized the significant public health issues caused by herpes simplex virus. The PHS publication, """"""""Healthy People 2010"""""""", has set sexually transmitted diseases as a national priority with a goal to reduce the number of adults infected with human papilloma virus and HSV-2.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI063820-04
Application #
7768492
Study Section
Special Emphasis Panel (ZRG1-IMM-K (12))
Program Officer
David, Hagit S
Project Start
2004-11-01
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
4
Fiscal Year
2010
Total Cost
$908,733
Indirect Cost
Name
Biomedical Research Models, Inc.
Department
Type
DUNS #
015341134
City
Worcester
State
MA
Country
United States
Zip Code
01606
Yang, Kejian; Varga, Steven M (2014) Mucosal vaccines against respiratory syncytial virus. Curr Opin Virol 6:78-84
Tirabassi, Rebecca S; Ace, Christopher I; Levchenko, Tatyana et al. (2011) A mucosal vaccination approach for herpes simplex virus type 2. Vaccine 29:1090-8