EXCEED THE SPACE PROVIDED. Infection of the genital tract by human papillomaviruses (HPVs) represents the most common sexually transmitted disease, resulting in squamous intraepithelial lesions (SIL) that can progress to cancer. Our continued overall goal is to understand the antibody responses to HPVs to better understand the natural history of infection and to aid in the design and evaluation of prophylactic vaccines, which are based on using virus-like particles (VLPs) to elicit protective neutralizing antibodies. We have learned a great deal about the response to HPV in naturally infected women.
One aim will be to determine whether the responses seen in vaccinated women are the same both quantitatively and qualitatively. We will follow the serum IgG reponses over time, and characterize the mucosal antibody response. We will determine whether the broad responses seen during natural infection also occur with vaccination. Another important goal will be to understand the antibody response in men. In a preliminary study we have studied a cohort of college men, similar to the women who have been intensively studied. Both the prevalence and titer of HPV 16 antibodies was Iowere in men, and seropositivity correlated better with past infection. It is important to learn more in a longitudinal study since responses may be different in men. Finally we are interested in charactering the epitopes that are recognized during natural and expermintal infection. Our preliminary dtata has found that a complex set of HPV 6 epitopes, largely tpye-specific, but some cross-reactive with HPV 11 are recognized. We would like to determine whether the same epitopes are recognized on other HPV types, both by making mutations in the surface exposed residues of HPV 16, and by transferring the putative epitopes of one type onto the backbone of a closely related, but immunologiclally distinct type. Not only will this information be useful in determining the generality of epitope recognition, but we also predict that we can construct multivalent VLPs that will be useful in comprehensive HPV vaccines. PERFORMANCE SITE ========================================Section End===========================================

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37AI038382-11
Application #
6832965
Study Section
Special Emphasis Panel (NSS)
Program Officer
Hiltke, Thomas J
Project Start
1995-05-15
Project End
2010-01-31
Budget Start
2005-05-01
Budget End
2006-01-31
Support Year
11
Fiscal Year
2005
Total Cost
$315,228
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Edelstein, Zoe R; Carter, Joseph J; Garg, Ruchi et al. (2011) Serum antibody response following genital {alpha}9 human papillomavirus infection in young men. J Infect Dis 204:209-16
Carter, Joseph J; Paulson, Kelly G; Wipf, Greg C et al. (2009) Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma. J Natl Cancer Inst 101:1510-22
Carter, Joseph J; Wipf, Greg C; Madeleine, Margaret M et al. (2006) Identification of human papillomavirus type 16 L1 surface loops required for neutralization by human sera. J Virol 80:4664-72
Buchinsky, Farrel J; Carter, Joseph J; Wipf, Gregory C et al. (2006) Comparison of oral fluid and serum ELISAs in the determination of IgG response to natural human papillomavirus infection in university women. J Clin Virol 35:450-3
Orozco, Johnnie J; Carter, Joseph J; Koutsky, Laura A et al. (2005) Humoral immune response recognizes a complex set of epitopes on human papillomavirus type 6 l1 capsomers. J Virol 79:9503-14
Onda, Takashi; Carter, Joseph J; Koutsky, Laura A et al. (2003) Characterization of IgA response among women with incident HPV 16 infection. Virology 312:213-21
Hagensee, M E; Koutsky, L A; Lee, S K et al. (2000) Detection of cervical antibodies to human papillomavirus type 16 (HPV-16) capsid antigens in relation to detection of HPV-16 DNA and cervical lesions. J Infect Dis 181:1234-9
Carter, J J; Koutsky, L A; Hughes, J P et al. (2000) Comparison of human papillomavirus types 16, 18, and 6 capsid antibody responses following incident infection. J Infect Dis 181:1911-9
Marrazzo, J M; Koutsky, L A; Stine, K L et al. (1998) Genital human papillomavirus infection in women who have sex with women. J Infect Dis 178:1604-9
Carter, J J; Galloway, D A (1997) Humoral immune response to human papillomavirus infection. Clin Dermatol 15:249-59

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