Under the Microscope: Vaccines for Victory

Vaccination—one of the greatest public health achievements in history—is based on a pretty simple idea. By exposing you to a harmless version of an agent that causes disease, a vaccine trains your body on how to defend against that disease. As a result, your immune system is poised to respond swiftly if it ever encounters the real deal.

In addition to stopping diseases such as polio, rinderpest, and smallpox in their tracks, vaccines can be turned against cancer. When a vaccine for human papillomavirus (HPV, the virus that causes 99.9 percent of cervical cancers) was released in 2006, for example, it raised the tantalizing possibility of eradicating cervical cancer altogether if enough people could be immunized.

While efforts to develop other cancer vaccines have hit roadblocks in the past, technological breakthroughs in recent years have sparked innovative new approaches. At the V Foundation, we believe cancer vaccines and other immunity-based approaches hold tremendous potential in the near term. With recent grants totaling $6 million, we are funding pivotal research that brings new hope for cancer prevention and cures.


A universal vaccine to stop EBV before it causes cancer

About 90 percent of the world’s adult population has been infected at some point with Epstein-Barr virus (EBV), which might cause no symptoms at all or may lead to full-blown infectious mononucleosis (“mono”). Although most recover from the infection itself, those with a compromised immune system due to HIV, malaria, organ transplant or other factors face a high risk of developing various types of cancers as a result of EBV.

It is the 200,000 people who receive a diagnosis of EBV-related cancers each year whom Javier Gordon Ogembo, PhD, is fighting for every day at his laboratory at the Beckman Research Institute of City of Hope, a leading cancer research and treatment center in Duarte, Calif.

Previous attempts at an EBV vaccine have failed because EBV uses several different proteins to cause infection. If only one is blocked, the virus can find another way in. To overcome this barrier, Ogembo used a V Foundation seed grant to develop a new virus-like particle that can hold many more proteins than the vectors used to develop previous vaccines.

Using this virus-like particle as a platform, Ogembo’s team developed an experimental EBV vaccine that contains all five of the most important proteins involved in EBV infection. The vaccine has proved to be effective in mice, and Ogembo is hopeful they can start clinical trials within a few years.

“Ultimately, we aim to create a universal vaccine that can be given to children zero to 5 years of age,” Ogembo said. “We have made remarkable progress. From the platform we developed and the data generated with our V Foundation grant, we were able to apply successfully for two R21 NIH grants. Our plan is to put all the data generated from the V Foundation and NIH funding together to bring this project to the next level.”

In parallel with their EBV research, the team is using this platform to pursue a vaccine for Kaposi sarcoma herpesvirus, another cancer-causing herpesvirus. Ogembo said vaccines developed with the platform could not only prevent cancer but also help boost the effectiveness of cancer immunotherapies like CAR T-cell therapy.


A promising therapeutic vaccine for a deadly childhood cancer

Vaccines are part of a broader class of biomedical advances that take advantage of the body’s natural defenses for both prevention and treatment. Texas Children’s Hospital physician-scientist Leonid Metelitsa, MD, PhD is using a vaccine-based approach to develop a new therapy for neuroblastoma, a cancer most commonly diagnosed in young children.

Metelistsa aims to induce patients’ immune systems to mount an attack against neuroblastoma cells. To do this, his team is adapting a strain of Salmonella bacteria that is similar to one used in an FDA-approved vaccine for typhoid.

“This type of bacteria is already given safely to humans, and it can be administered orally,” Metelitsa explained. “What we needed to do is engineer this bacteria to carry genetically engineered tumor-associated antigens.”

It was a tricky proposition to create a strain strong enough to trigger an immune response capable of destroying cancer. At the same time, the strain needed to target exactly the right protein, or antigen, to allow the immune system to zero in on cancer cells.

Key to the experimental vaccine’s promise is that it targets MYCN, a protein that is involved in tumor creation and is not found on other types of cells in the body. By targeting this specific protein, the researchers believe their vaccine can trigger an immune reaction that is specific to neuroblastoma without major side effects, allowing young patients to get back to a normal—and healthy—life.

The team anticipates beginning clinical trials by 2020.