From Agriculture to Virology: The Accidental Vaccine Developer

March 23, 2018 | by Katie Neith

Experimental Therapeutics - Javier Gordon Ogembo Javier Gordon Ogembo, Ph.D.
“I like to say that I’m the only trained farmer at a medical institution,” said Javier Gordon Ogembo, Ph.D., assistant professor in the Department of Immuno-Oncology, who joined City of Hope in 2016.
 
It may sound like hyperbole, but he’s not stretching the truth. With undergrad training in horticulture, a master’s degree in entomology and a Ph.D. in agriculture, Ogembo more or less stumbled into medicine — and based on his successes over the past two years at City of Hope, the field is lucky to have him.
 
“The mentorship and support I have received from City of Hope senior researchers such as Don Diamond, John Zaia and Larry Kwak has exceeded my expectations,” said Ogembo. “Because of the superb environment, we have been able to bring aboard three very talented postdoctoral fellows — Lorraine Mutsvunguma, Murali Muniraju and David Mulama — and a research associate, Joslyn Foley, who are working tirelessly to develop and test our novel vaccine candidates.”
 
Although Ogembo is working on the development of vaccines against oncogenic viruses, he never had any plans to work in medicine when he was in school. Originally from Kenya, he traveled around the world, picking up agriculture-related degrees and experience in places like Zimbabwe, England and Japan. But when a postdoctoral mentorship opportunity at University of California Berkeley fell through, Ogembo found himself unexpectedly searching again for a fellowship. That pursuit led him to Harvard Medical School, where he decided to give a virology job in the Department of Medicine a shot.
 
“I wasn’t sure why they selected me, but it worked out,” said Ogembo. “And during that transition, a very remarkable type of thing took place: My mom was diagnosed with cervical cancer.”
 

A Call to Action

He said that experience — in which his mother was misdiagnosed, a discovery made just before she was to go in for major surgery — drove his interest in studying cancer. When he found out that cervical cancer is caused by a virus, it helped solidify his career path.
 
When I was doing entomology, I was studying DNA viruses that infect insects,” explained Ogembo. “And all the cancer-causing viruses are DNA viruses, so they are very similar to the insect viruses I was studying. It was a very easy translation from one area to the other.”
 
The particular viruses that he now studies are the Epstein-Barr virus (EBV), best known for causing mononucleosis, or “mono”; the Kaposi sarcoma-associated herpesvirus (KSHV); and human papillomavirus (HPV), the causative agent of cervical cancer.
 
Currently three vaccines to prevent HPV are already on the market, so Ogembo is focused on developing a new therapeutic HPV vaccine that’s able to treat those already infected. However, a big ethical question on the use of prophylactic vaccines, he said, is how to integrate the new nonavalent (treating nine strains) vaccine with the previously existing ones that treat two (bivalent) or four (quadrivalent) strains. 
 
“It’s a big challenge, particularly because the prophylactic vaccine is given at a young age under the assumption that the recipients have not yet been sexually active — but what if they’re already infected?” said Ogembo. “We think that there should be another line of protection, so that’s the idea that I’m working on. I’m working in collaboration with the Department of Pathology to retrieve all the invasive cervical cancer tissues archived here and now we are sequencing all the viruses — every strain — that are in there, as well as the human genome.”
 
"And that’s because, he said, "it appears that high-risk HPV genotypes that cause cervical cancer are associated with certain ethnicities. So, if HPV is causing cancer within an ethnic community, it’s likely a particular strain," according to Ogembo. The clinical implication of this in the diagnosis and management of patients is unknown. His goal is to see if there’s a correlation between ethnicity, the type of strains and mutations, and the outcome of viral infection. Then, if correlations do exist, he plans to use that information to make a vaccine that is universal.
 
“It’s easier said than done, but it’s what we’re trying to do,” said Ogembo.

Taking Preventive Measures

EBV is another tricky pathogen, considered oncogenic — or cancer-causing — because it can cause several types of lymphomas, particularly in organ transplant patients and other immunocompromised people. There have been unsuccessful attempts by others to develop a vaccine against this common virus, but by improving upon a previously invented platform for delivering vaccines, Ogembo believes he has a better way of delivering an EBV vaccine. He has seen promising results in animal models and recently filed a patent for antibody-peptide conjugates that can treat EBV-associated post-transplant lymphoproliferative diseases.
 
Like the vaccine that already exists for preventing HPV, the platform uses a virus-like particle to deliver a viral protein that leads to the generation of antibodies capable of blocking infection. But Ogembo’s model adds more than one viral protein, to not only generate antibodies but also induce cellular T cell immune responses, potentially boosting the vaccine’s efficacy. The Stop Cancer Foundation has providing funding to fine-tune the development of the EBV vaccine and to support preclinical testing.
 
What we’ve done, which we think is clever, is we are packaging multiple viral glycoproteins involved in viral entry into the host cell, thus generating potent antibodies capable of blocking infection,” said Ogembo. “And we’ve found they are very immunogenic. We’ve simply made a good thing better.”
 
Ogembo is using the same platform to tackle a KSHV vaccine. In fact, he also recently filed a patent on strategies for developing multivalent EBV and KSHV vaccine candidates. And a recent recruit to his lab, postdoctoral fellow David Mulama, Ph.D., received a three-year, $330,000 grant this past November from the St. Baldrick's Foundation to support his work on a vaccine for KSHV and help advance his goal of developing a diagnosis and prevention method for fighting pediatric Kaposi sarcoma in his home country of Kenya. KSHV infection can lead to Kaposi sarcoma, a cancer that usually appears as tumors on the skin or mucosal surfaces and presents as an AIDS-related malignancy. But in certain parts of the world, such as Africa, it is endemic, particularly in older men with or without immunosuppression.
 
“In the U.S., infection rates for KSHV are 1 to 4 percent, but in Africa, depending on the region, it could be 30 to 60 percent,” said Ogembo. “This difference actually gives a good platform for proving a vaccine works, because in the U.S., there are pockets where you could vaccinate and herd-immunity would wipe it out. If you have a model that’s successful, then you can go to Africa knowing you can reduce the cases. The platform that we are developing can give us a good tool for also developing vaccines against other oncogenic viruses.”
 
In other words, he’s hoping to take the discoveries he’s making about how to immunize against these oncogenic viruses and apply them to even more cancer-causing pathogens in a clinical trial.
 
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