Vaccine Research Center

Three different HIV antibodies each independently protected monkeys from acquiring simian-HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform development of a preventive HIV vaccine for people. The antibodies -- a human broadly neutralizing antibody and two antibodies isolated from previously vaccinated monkeys -- target the fusion peptide, a site on an HIV surface protein that helps the virus fuse with and enter cells. Three different HIV antibodies each independently protected monkeys from acquiring simian-HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform development of a preventive HIV vaccine for people. The antibodies -- a human broadly neutralizing antibody and two antibodies isolated from previously vaccinated monkeys -- target the fusion peptide, a site on an HIV surface protein that helps the virus fuse with and enter cells. The study, published in Science Translational Medicine, was led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Antibodies that target the fusion peptide can neutralize diverse strains of HIV in vitro, that is, in a test tube or culture dish outside of a living organism. The NIAID VRC isolated a fusion peptide-directed human antibody, called VRC34.01, from a person living with HIV who donated blood samples for research. They also isolated two antibodies from rhesus macaques -- a species of monkey with immune systems like humans' -- who previously had received a vaccine regimen designed to generate fusion peptide-directed antibodies. Demonstrating that these antibodies protect animals would validate the fusion peptide as a target for human vaccine design. SHIV challenge -- administering an infective dose of SHIV -- to rhesus macaques is a widely used animal model for assessing the performance of HIV antibodies and vaccines. In this study, rhesus macaques in each of four groups received a single intravenous infusion of one type of antibody -- a 2.5 or 10 mg/kg of bodyweight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies -- and other monkeys received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after infusion with a strain of SHIV known to be sensitive to fusion peptide-directed antibodies. All monkeys that received a placebo infusion acquired SHIV following the challenge. Among monkeys that received VRC34.01 infusions, none receiving the 10 mg/kg dose and 25% of those receiving the 2.5 mg/kg dose acquired SHIV. Of those that received the vaccine-elicited rhesus macaque antibodies, no monkeys receiving the antibody called DFPH-a.15 acquired SHIV, and 25% of those receiving the antibody called DF1W-a.01 acquired SHIV. Over time, the concentration of antibodies in the blood of animals that received DFPH-a.15 declined. Those animals were re-challenged 30 days later to see if the lower concentration of antibodies had a decreased protective effect, and half of them acquired SHIV. The three antibodies studied each provided statistically significant protection from SHIV, and the effect was dose dependent, that is, highest in monkeys with greater antibody concentrations in their blood. According to the authors, these findings represent the proof-of-concept that fusion peptide-directed antibodies can provide protection against SHIV and help determine the concentration of antibodies a vaccine would need to generate to be protective. They suggest that their findings on vaccine-elicited antibodies in some animals support further work to design preventive HIV vaccine concepts targeting the fusion peptide. They conclude that an effective HIV vaccine targeting the HIV fusion peptide likely will need to expand upon the concepts used in this study, by generating multiple varieties of fusion peptide-directed antibodies. This would increase the likelihood that the vaccine could maintain a preventive effect across the vastly diverse HIV variants in circulation.

The US National Institutes of Health (NIH) on Wednesday announced that Jeanne Marrazzo has been selected to run the National Institute of Allergy and Infectious Diseases (NIAID). The incoming director, currently head of the infectious diseases division at the University of Alabama, takes up her new role in the fall and succeeds Anthony Fauci, who led the NIH unit for 38 years before stepping down last December.With an annual budget of $6.3 billion, NIAID is the second largest of the NIH's 27 institutes and centres, after the National Cancer Institute. Acting NIH director Lawrence Tabak stated that Marrazzo "brings a wealth of leadership experience from leading international clinical trials and translational research, managing a complex organisational budget that includes research funding and mentoring trainees in all stages of professional development."Her scientific work has focused on the human microbiome, specifically as it relates to female reproductive tract infections and hormonal contraception, as well as the prevention of HIV infection using biomedical interventions, including PrEP and microbicides, and the pathogenesis and management of bacterial vaginosis, sexually transmitted diseases in HIV-infected patients and management of antibiotic resistance in gonorrhoea.NIAID supports research at universities and research organisations around the US and across the unit's 21 laboratories, including the Vaccine Research Center where Ted Pierson was recently appointed director. It is also mandated to respond to emerging and re-emerging public health threats in the US and abroad. Hugh Auchincloss has been acting director of NIAID since Fauci's departure at the end of last year. The NIH can install Marrazzo in the post without a presidential appointment or confirmation by the US Senate.Meanwhile, the Biden administration has not been able to secure a permanent appointment to run the broader NIH agency after long-time director Francis Collins stepped down at the end of 2021. Monica Bertagnolli was nominated in May, but Senator Bernie Sanders has said he will not hold a hearing on any health nominee until he sees a "robust" plan from the White House about lowering drug prices.

WEDNESDAY, Aug. 2, 2023 -- Dr. Jeanne Marrazzo was named on Wednesday to become the next head of the U.S. National Institute of Allergy and Infectious Diseases, a job most recently held by Dr. Anthony Fauci , well known for his work on HIV and the pandemic. Marrazzo will start her new job in the fall. She is currently the director of the Division of Infectious Diseases at the University of Alabama at Birmingham. “Dr. Marrazzo brings a wealth of leadership experience from leading international clinical trials and translational research, managing a complex organizational budget that includes research funding and mentoring trainees in all stages of professional development,” Dr. Lawrence Tabak , acting director for the U.S. National Institutes of Health (NIH), said in an NIH news release . “I look forward to welcoming Dr. Marrazzo to the NIH leadership team.” NIAID’s role is in conducting and supporting research to better understand, treat and prevent infectious, immunologic and allergic diseases. Marrazzo’s background includes research on the human microbiome and its role in female reproductive tract infections and hormonal contraception, preventing HIV using biomedical interventions and management of bacterial vaginosis, sexually transmitted diseases in HIV-infected persons and management of antibiotic resistance in gonorrhea. She has been a principal investigator on NIH grants since 1997. Marrazzo has also mentored countless trainees, including on NIH-funded training grants. Her appointment was lauded by those in the medical community. Fauci told CNN she was a “good person,” and would likely face big challenges at NIAID. “What she’s facing now is going to be a very complicated issue of a number of emerging diseases, a high degree of advanced technology that is really an important part of the research effort on infectious diseases. Also, she’s going to be dealing with, you know, unfortunately, as we’ve seen over the last few years, a very divisive political setting, where there’s been an unfortunate politicization of some of the science,” Fauci added. Luckily, Marrazzo loves tough challenges, Dr. Carlos del Rio , interim dean of the Emory University School of Medicine and president of the Infectious Diseases Society of America (IDSA), told CNN . “She’s a remarkable physician, researcher and advocate,” del Rio said. “She has a long history of work on sexually transmitted infections and on HIV prevention. And she is a great listener, a great person and has a superb personality. I mean, I’m just thrilled. She is an excellent person for this job,” said del Rio, who meets with Marrazzo regularly as part of the IDSA board. Marrazzo received the American Sexually Transmitted Diseases Association’s Distinguished Career Award, which is the highest recognition of contributions to research and mentoring in the field. Her education includes a bachelor’s degree in biology from Harvard University; a Master of Public Health in Epidemiology from the University of Washington in Seattle, and an MD from Thomas Jefferson University in Philadelphia. The new director will oversee NIAID’s $6.3 billion budget. The agency has 21 labs, including the Vaccine Research Center on NIH’s main campus in Bethesda, Md. It also responds to emerging public health threats in the United States and globally. Sources U.S. National Institutes of Health, news release, Aug. 2, 2023 CNN Posted August 2023