In Search of the Elusive Vaccine for HIV

How a recent biology alumna is working toward a vaccine that would protect people from one of the world’s deadliest and most feared viruses

Immediately following her graduation last May, Christina Rosario ’17 was hired as a research specialist with a team at University of Pennsylvania School of Medicine working toward developing a vaccine for HIV.

“During the interview process, I was told that one of the reasons I stood out from other applicants was because of the small school I came from,” she says. “Small class sizes and connections with professors and other classmates showed that I had the opportunity to fully understand and be engaged in all of my biology courses.”

Professor Jean Shingle, Ph.D., taught Rosario’s molecular biology class at IU and provided the one-on-one assistance that helped Rosario master skills critical to the work she is doing now: understanding, interpreting, and presenting research. “As a research specialist, I am expected to translate what I learn from different research articles into each experiment that I perform and analyze.”

Why HIV is tough to fight

The antibodies in our immune systems are designed to identify and mark certain pathogens for neutralization. Our white blood cells then sound the alarm and attack the infectious organism.

HIV presents two main challenges to our immune systems. First, HIV targets CD4 cells, which are one type of the very white blood cells that are supposed to mobilize our defensive mechanisms. The virus uses a specific protein, glycoprotein 120, on its outer coating to bind to CD4 cells, destroy them, and use them to reproduce and spread. In most cases, our antibodies are not strong enough to overcome the virus, which is then able to disperse and undermine our immune systems.

Second, the virus mutates rapidly, and its genetic makeup can vary widely. This not only makes it harder for our bodies to identify numerous forms of HIV as a threat; it also makes vaccine development difficult. Vaccines introduce an inactive pathogen to the body, allowing the immune system to recognize it as an invader and generate antibodies that are prepared to target a real infection with the same pathogens later on. Researchers have to find a way to create a vaccine that helps the body recognize and attack as many strains of HIV as possible.

The promise of broadly neutralizing antibodies

In rare cases, however, people with HIV can produce broadly neutralizing antibodies, or bNAbs, which can kill a wide range of HIV strains, sometimes up to 90 percent of different types. Most antibodies can neutralize only one or a few types of infections. But bNAbs bind to the glycoprotein 120 site on the HIV outer coating, which prevents the virus from attaching to the body’s CD4 cells, leaving them free to rally the immune system to fight the infection.

Researchers believe that knowing more about how bNAbs work may provide the key to creating a vaccine that combines the power of these antibodies to be effective against many variations of HIV.

In 2016, HIV and related complications caused one million people to die worldwide.
(Source: World Health Organization)

About 36.7 million people were HIV-positive at the end of 2016.
(Source: World Health Organization)

Around the world, 1.8 million people became infected with HIV in 2016.
(Source: World Health Organization)

More money has been spent on developing an HIV vaccine than on the development of any other vaccine to date.
(Source: WebMD)

The research process

Rosario’s lab at Penn Medicine is receiving a $16.3 million grant over five years from the National Institute of Allergy and Infectious Diseases to study the development of bNAbs in rhesus macaque monkeys infected with various strains of simian-human immunodeficiency virus (SHIV), a version of HIV that affects monkeys. The research team is focusing on SHIV variants that provoke a strong immune reaction in the monkeys, generating both strain-specific and broadly neutralizing antibodies.

What triggers the immune system to produce bNAbs is still somewhat unclear, so Rosario and her team are analyzing the molecular events involved in this process. This will give them clues about how to design a vaccine that will elicit the bNAbs the immune system needs to fight off future HIV infections.

Rosario’s day-to-day responsibilities in this project include tissue and cell culturing, processing SHIV-infected monkey blood, and conducting experiments using the plasma extracted from that blood to discover to what extent the antibodies have neutralized different strains of viruses. Rosario’s tests examine common strains of HIV found around the world as well as various SHIVs. Using specific protocol and calculations, she generates graphs that show if a specific strain was neutralized or not.

“Processing this infected blood is one of the most important parts of this research project,” Rosario says, “because it allows us to perform many other experiments in the realm of broadly neutralizing antibodies,” such as genome sequencing.

After she fulfills her role on this research team, Rosario hopes to attend medical school and work with patients who are HIV-positive or who have infectious diseases. “I would like to work with and help those in underdeveloped and impoverished areas that don’t have the resources they need to prevent or properly manage their HIV/AIDS and/or other health problems,” she says.

For now, though, she says, “I often find myself taking a second to think about how lucky I am to be a part of this groundbreaking research. The one thing I have always wanted for myself was a career that is both meaningful, while at the same time contributing to society in a positive way, and I like to think that I have fulfilled that goal.”

Author: aduncan

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