Worldwide, 15% of all cancer cases and nearly 25% of cancer cases in developing countries are attributable to viruses. Human cancers associated with virus infection include human papillomavirus, human T-cell leukemia virus type 1, Epstein-Barr virus, hepatitis B virus, hepatitis C virus, and Kaposi's sarcoma-associated human herpesvirus (KSHV). Of these, KSHV is the leading cause of death in HIV-infected individuals. Infection of KSHV is estimated to account for 34,000 new cancer cases globally. Efforts to develop a KSHV vaccine are limited, due to lack of animal model to test the potential vaccine candidates. Through collaborations, we now have access to common marmosets, a non-human primate model that support KSHV infection and develop skin lesions typical in infected individuals. We have also developed a virus-like particle platform to display KSHV envelope glycoprotein antigens as candidate vaccines that has potential to prevent or treat KSHV infection and its associated malignancies.

Public Health Relevance

Several human cancers are attributable to viruses. Every year, Kaposi's sarcoma-associated human herpesvirus (KSHV) accounts for 34,000 new cancer cases worldwide. We propose to use a combination of novel virus-like particles, labeled KSHV, and newly developed animal model to study how KSHV infection occurs. Our findings will be essential to developing new therapeutics and vaccines to treat and prevent KSHV- associated diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
7K01CA184388-03
Application #
9124807
Study Section
Subcommittee I - Transition to Independence (NCI-I)
Program Officer
Chung, Davyd W
Project Start
2014-08-05
Project End
2019-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
3
Fiscal Year
2016
Total Cost
$108,808
Indirect Cost
$6,386
Name
Beckman Research Institute/City of Hope
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
Barasa, Anne K; Ye, Peng; Phelps, Meredith et al. (2017) BALB/c mice immunized with a combination of virus-like particles incorporating Kaposi sarcoma-associated herpesvirus (KSHV) envelope glycoproteins gpK8.1, gB, and gH/gL induced comparable serum neutralizing antibody activity to UV-inactivated KSHV. Oncotarget 8:34481-34497
Perez, Elizabeth M; Foley, Joslyn; Tison, Timelia et al. (2017) Novel Epstein-Barr virus-like particles incorporating gH/gL-EBNA1 or gB-LMP2 induce high neutralizing antibody titers and EBV-specific T-cell responses in immunized mice. Oncotarget 8:19255-19273
Weiss, Eric R; Alter, Galit; Ogembo, Javier Gordon et al. (2017) High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis. J Virol 91:
DeGregorio, Geneva A; Bradford, Leslie S; Manga, Simon et al. (2016) Prevalence, Predictors, and Same Day Treatment of Positive VIA Enhanced by Digital Cervicography and Histopathology Results in a Cervical Cancer Prevention Program in Cameroon. PLoS One 11:e0157319
Pelowski, Matthew; Wamai, Richard G; Wangombe, Joseph et al. (2016) How Would Children Register Their Own Births? Insights from a Survey of Students Regarding Birth Registration Knowledge and Policy Suggestions in Kenya. PLoS One 11:e0149925
Ogembo, Javier Gordon; Muraswki, Matthew R; McGinnes, Lori W et al. (2015) A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice. J Transl Med 13:50