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IV Drug Users & HIV Vaccine Response

Monday, June 12, 2017

Prevention strategies such as Treatment as Prevention, PrEP, syringe exchange, and public awareness have helped to reduce the global number of new HIV infections over the past fifteen years by thirty-five percent. Despite these advances, the rate of new HIV infections in 2015 was an alarming 2.1 million and continues to rise among certain high-risk groups. As such, an effective, universal preventative vaccine (that can also be used as a therapeutic vaccine) is likely the only course in permanently stopping the spread of HIV worldwide and fulfilling the elusive dream of an “HIV-free generation.”

However, new research may indicate that the current course of vaccine research may lead to a preventative vaccine that is ineffective for an entire high risk population, thus delaying efforts to eradicate HIV.

Research conducted by Dr. James Kobie and his team at the University of Rochester, found that intravenous drug users (IVDUs) have severe differences in their immune system that could potentially limit their development of the same protection conferred by a potential HIV preventative vaccine as the general population. Dr. Kobie compared the blood of nineteen HIV-negative, active intravenous drug user volunteers to nineteen HIV-negative, non-drug using individuals. Over 100 different aspects of the participants’ B cells and antibodies were measured.

Dr. Kobie and his team found that B cells of the IVDU participants differed substantially from the non-IVDU participants. The IVDU groups’ B cells showed signs of over-activity, suggesting more frequent stimulation of immune responses. The exact cause of this stimulation is yet unknown. However, researchers also discovered high levels of endotoxins in the blood of some of the IVDU participants. An endotoxin is a toxin that sits in the outer wall of some bacteria and its release into the body can elicit a B-cell response. In addition, large numbers of cytokines that can cause inflammation were also found.

Intravenous drug users often experience a larger number of infections, sometimes generating from injection sites, as well as reactions to impurities contained in the injected drug. These may also cause a degree of immune activation.

Highly effective vaccines most often depend on successful B-cell and antibody responses and these responses can be compromised if an individual’s immune system is already overtaxed. Does this mean that an HIV vaccine may not prove to have the same efficacy in IDVUs as it might in other populations? The answer remains to be determined. However, it has been previously shown that IVDUs have a reduced response to hepatitis A and hepatitis B vaccines, meaning that a reduced response to an HIV vaccine is conceivable.

“If we fail to appreciate differences in the immune response of injection heroin users, we may develop an HIV vaccine that fails to protect against a growing vulnerable population,” stated Dr. Kobie.

Although this is one small study and follow-up studies are needed to confirm the results, Dr. Kobie’s research is a reminder of the importance of continued funding for HIV research that is inclusive of all populations, such as IVDUs, especially as we know that the rate of opiate addiction in the United States is skyrocketing. According to the World Drug Report 2016 released by the UN Office on Drugs and Crime, the use of heroin in the U.S. is at its highest point in the past twenty years, with an estimated 1 million heroin users in 2014. Rates of heroin addiction have drastically increased particularly among whites aged eighteen to forty-four and people living on lower incomes.

Read More: IV Drug Users & HIV Vaccine Response

Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques

Tuesday, February 21, 2017

Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig) purified from previously infected animals (SHIVIG) or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

Read More: Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques

Dr. Kobie and Dr. Keefer on Reddit HIV Vaccine AMA

Thursday, February 9, 2017

Science AMA Series: We’re Drs. Michael Keefer and James Kobie, infectious disease researchers at the University of Rochester Medical Center in Rochester, New York. We’re working to find new ways to develop a vaccine to prevent HIV. Ask Us Anything!

Read More: Dr. Kobie and Dr. Keefer on Reddit HIV Vaccine AMA