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Antibodies As a Potential Fix to HIV/AIDS—Interview with Adrian McDermott, Acting Chief of the Immunology Core in the NIH’s Vaccine Research Center

by Sara Malmanger, University of Wisconsin-Madison, Science Writing Intern with BioQuick News

HIV researchers have found that giving the human body’s immune system a boost of specific antibodies may be a potential fix to HIV/AIDS as we seek a cure or vaccine. Our world could be free of this deadly virus sooner than we ever thought possible. Researchers are hopeful that they have found a way to turn our own immune systems against the disease. In an interview, Adrian McDermott (photo), PhD, from the NIH’s Vaccine Research Center, said, “We are hoping to use HIV-specific antibodies that target vulnerable parts of the HIV envelope to prevent and treat HIV.” The Vaccine Research Center is within the NIH’s National Institute of Allergy and Infectious Diseases, and Dr. McDermott is presently Acting Chief, Immunology Core, within the Vaccine Research Center. He is a former Director of Immunobiology and Vaccine Design at the International AIDS Vaccine Initiative (IAVI) in New York. The antibody studies are important because more than 35 million people have HIV worldwide, and around one million people have HIV in the United States. Despite the common feeling that AIDS (acquired immunodeficiency syndrome) is a disease of the past, it is still harming and destroying many lives. HIV (human immunodeficiency virus) essentially erodes and ultimately destroys the immune system over time. HIV, without appropriate health care and treatment, can develop into AIDS. Once a person reaches the AIDS stage of the infection, the immune system can’t fight off pathogens that cause common illnesses, where a healthy immune system could knock these bugs out with ease.

Opportunistic infections that are innocuous or mild in healthy individuals are frequent and often fatal in a people with AIDS because their immune systems are deteriorated, and unable to fight back. These infections include pneumocystis pneumonia and infections caused by cytomegalovirus (CMV, a herpes virus). Kaposi’s sarcoma, caused by Kaposi’s sarcoma-associated herpes virus (HHV-8), is also frequently seen in AIDS patients and rarely in healthy individuals. These are just a few examples of the many illnesses that often cause death in AIDS patients.

A study published on November 15, 2016 in the PLOS ONE science journal investigates the use of vaccines to elicit the production of antibodies and cellular immunity against HIV. The article is titled “Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012),” and Dr. McDermott was one of the co-authors. (http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166393).

This study investigates the results of immunization using a particular adenovirus platform/vehicle (the recombinant adeno virus rAd35) coupled to an HIV antigen (the virus envelope protein EnvA). The goal was to determine if this particular adenovirus platform might be less complicated by the pre-existence of anti-adeno antibodies and might lead to an enhanced antibody and cellular immune response to the HIV protein EnvA.

While the study showed that the adeno-platform-EnvA was safe and immunogenic, improvements in the combination of platform and strategy have, in some other cases, produced more robust antibody (humoral) and cellular immune responses to candidate vaccines than those observed in the study published in PLOS ONE. “However, the goal of broad and potent protection against infection with multiple pathogens, including HIV, remains elusive,” the authors stated.

“Several other groups have tested rAd35-EnvA as a boost, some with encouraging results. That data complements our finding that rAd35-EnvA is immunogenic as a boost in a heterologous regimen in subjects seronegative for Ad5, and suggests that rAd35 may indeed be useful in overcoming pre-existing adenoviral immunity,” the authors concluded.

Dr. McDermott’s past experiences with HIV/AIDS largely influence his research efforts now.

As he traveled around to numerous universities, cities, hospitals, and research centers throughout his career, Dr. McDermott gained valuable experience with HIV/AIDS research, treatment, and prevention. His interest in virology and immunology led him to his first job at a London hospital, which along with many other positions, paved the way to motivating the research he has done to contribute to many HIV/AIDS advancements.

These contributions include work done in the early 90s on the early diagnosis of HIV in new-born infants, examining the relationship between CD8 T cells and virus evolution in nonhuman primates, laboratory assessments for testing prototype HIV vaccines, and the use of HIV-envelope-specific antibodies in HIV-positive and HIV-negative individuals.

In the late 1980s, finding a reliable HIV test was key to early diagnosis, although treatment was only palliative. The impact on potentially infected individuals fearing that they were HIV-positive was confusion, as tests were unreliable and the clinics tried to avoid misdiagnoses. In these early days of the epidemic, counseling, performed nowadays by trained psychologists, was largely unavailable and practices were not standardized to prevent the obvious anxiety associated with HIV testing. Today, HIV testing is a routine procedure with maximum compassion and safeguards built into the process of counseling and conveying the outcomes.

As time went on, the tests for HIV became more specific and reliable. The early 1990s brought along HIV clinics that offered same-day diagnosis and counseling by nurses. These types of clinics gained immense popularity and started to expand.

After college and before getting his PhD at University College London, McDermott was involved in the communication of patient results at the Royal Free Hospital in London. Correctly informing patients of their status allows them to get the right treatment and know how to alter risk behavior to decrease their chances of spreading the virus. The language and standard practices in conveying the news of “reactive” or “non-reactive” tests were relatively crude, yet designed to alleviate anxiety and to reduce the emotional stress that a diagnosis usually brings with it.

Working in HIV outreach and at research universities in New York and San Francisco, Dr. McDermott gained a different perspective on the HIV pandemic. In California at the University of California-San Francisco (UCSF), he worked with researchers and advocates, learned the politics of HIV, and discovered how HIV funds were raised through the governmental and non-for-profit organizations.

Subsequently, Dr. McDermott came to the University of Wisconsin (UW)-Madison campus in 2001 and worked alongside Drs. Matt Reynolds, David O’Connor, and Tom Friedrich, current professors at UW-Madison, to improve the model of HIV vaccines. This model was greatly improved by doing work with nonhuman primates such as
rhesus macaques. Much of the important work that this successful team did in the early 2000s led to what we know about how HIV escapes the immune response in infected individuals.

“The role of UW in the search for an AIDS vaccine has often been underestimated,” said Dr. McDermott.

Dr. McDermott is looking to get people the best protection against HIV and create consumable or injectable anti-HIV antibodies that can be taken once every few months. These drugs may provide long lasting-relief and could be administered less often than the everyday pills currently used for HIV prevention and control.

Dr. McDermott professionally dreams of contributing to off-the-shelf HIV and other infectious agent vaccines that can save many people. Dr. McDermott’s lifelong enthusiasm and dedication to HIV/AIDS research has led to major advancements in vaccine development.

[PLOS ONE article]