Cross clade immune responses found in South Africa from the RV144/Thai HIV vaccine regimen

SEATTLE, SEPTEMBER 18, 2019 – The results of the study called HVTN 097, titled “Immune correlates of the Thai RV144 vaccine regimen in South Africa” and led by Dr. Glenda Gray, Co-Principal Investigator of the HIV Vaccine Trials Network (HVTN), headquartered at the Fred Hutchinson Cancer Research Center and funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and President of the South African Medical Research Council (SAMRC), were published in the journal Science Translational Medicine on September 18. This study was conducted in South Africa using the same HIV vaccine regimen that showed modest protection in an efficacy study conducted in Thailand, where clades B and E are prominent. Although clade C is the dominant circulating strain of HIV in South Africa, the RV144/Thai vaccine regimen mounted significant cellular and antibody responses in study participants enrolled in South Africa.

Despite major breakthroughs in HIV prevention and treatment, there were an estimated 1.8 million people newly infected with HIV in 2018: an estimated 5,000 new HIV infections around the world every day. The pursuit for a safe, effective and scalable HIV vaccine, although a challenging endeavor, is a global imperative.

Gray and her team evaluated whether the vaccine-induced immune responses would be similar in a South African cohort if immunized with the same RV144 HIV vaccine regimen used in Thailand. The U.S. Army-led RV144 was the first vaccine clinical trial to ever demonstrate any efficacy in preventing HIV that tested a heterologous “prime-boost” combination of two vaccines: ALVAC-HIV and AIDSVAX B/E vaccine based on clades B and E, which demonstrated moderate protection against HIV with a 31.2% efficacy.

“Vaccine-induced immune responses elicited from this clade B/E based vaccine regimen induced cross-clade responses in South Africans and, at peak immunogenicity, the South African vaccinees exhibited significantly higher cellular and antibody immune responses than the Thai vaccinees,” said Gray.

The HVTN 097 study is part of a larger HIV vaccine research endeavor led by the Pox-Protein Public-Private Partnership, or P5–a diverse group of public and private organizations committed to building on the success of the RV144 trial. The P5 aims to produce an HIV vaccine that could have a significant public health benefit in southern Africa and to advance scientists’ understanding of the immune responses associated with preventing HIV infection. P5 members include the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, Bill & Melinda Gates Foundation, South African Medical Research Council (SAMRC), HVTN, Sanofi Pasteur, GSK and the U.S. Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research. NIAID funds the HVTN and funded the HVTN 097 study.

“Since 2009, the HIV vaccine field has been building on findings from RV144 to understand and develop improvements in vaccine breadth and duration in order to protect more people for longer periods of time,” said Lt. Col. Julie Ake, Principal Deputy Director of MHRP.

T-cell and antibody responses measured

The RV144 vaccine regimen in HVTN 097 vaccinees induced a significantly higher CD4+ T cell response rate than seen in the Thai vaccine recipients (RV144=36.4%; HVTN 097=51.9%), irrespective of age and sex. South African and Thai participants also generated cross-clade antibody responses against HIV clades AE, B, and C, which, in a panel of clade C antigens, were also higher and more prevalent in South Africans. In general, cross-clade immune responses were stronger than expected in South Africa. HVTN 097 is a precursor to studies that adapted the RV144/Thai vaccine regimen to be clade C specific, now underway in South Africa (HVTN 702).

“This breaks open the thought pattern that each region of the world needs a separate type of HIV vaccine based upon their circulating strains,” said Larry Corey, M.D., Principal Investigator of the HVTN.

Associations between BMI and vaccine-induced immune responses

A previous clinical trial (HVTN 503/Phambili) conducted in South Africa demonstrated that higher BMI was associated with a reduction in vaccine-induced immune responses. Given the high rates of obesity in South Africa, the HVTN 097 study team, after stratifying the groups, found that a higher BMI was not associated with a reduced CD4+ T cell and antibody response rate or the strength of the response rate. Notably, CD4 + T cell responses were detected in 100% of vaccinees with a BMI greater than 30, giving hope for future HIV vaccine regimens based on the RV144/Thai vaccine regimen.

Differences observed in vaccine-induced immune responses between Thais and South Africans

The study team acknowledge that factors such as race, ethnicity, the microbiome, or genetic factors may have influenced vaccine-induced immune responses in South Africans.

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Competing interests and source funding:

The authors declare that they have no competing interests.

The HVTN 097 clinical trial was supported by the National Institute of Allergy and Infectious Diseases (NIAID) U.S. Public Health Service grants UM1 AI068614 (LOC: HIV Vaccine Trials Network), UM1AI068618 (LC: HIV Vaccine Trials Network), UM1 AI068635 (SDMC: HIV Vaccine Trials Network), UM1 AI069453 (Soweto-Bara Clinical Research Site), UM1 AI069519 (Cape Town-Emavundleni Clinical Research Site), and UM1 AI069469 (Klerksdorp Clinical Research Site). Within the terms of the Grant Award of the Cooperative Agreement with the HVTN, NIAID, as protocol sponsor, contributed to, reviewed, and approved the HVTN 097 study design. NIAID contributed to review and analysis of data, and preparation of the manuscript, and concurred with the decision to submit for publication, but was not involved in the data collection and did not perform statistical analyses. NIAID provided support in the form of salary for author E.M.S. No pharmaceutical company or other agency paid for the writing of this article. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. We thank the James B. Pendleton Charitable Trust for their equipment donation. Additional funding for laboratory assays was provided by the South African Medical Research Council (SAMRC), and we thank the Bill & Melinda Gates Foundation for their generous contribution to the Cape Town HVTN Immunology Laboratory facility. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or NIH. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense.

Authors:

Glenda E. Gray, MBBCH, Ying Huang, PhD, Nicole Grunenberg, MD, Fatima Laher, MBBCh, Surita Roux, MBChB, Erica Andersen-Nissen, PhD, Stephen C. De Rosa, MD, Britta Flach, PhD, April K. Randhawa, PhD, Ryan Jensen, PhD, Edith M. Swann, PhD, Linda-Gail Bekker, MD, PhD, Craig Innes, MBChB, Erica Lazarus, MBChB, Lynn Morris, DPhil, Nonhlanhla N. Mkhize, PhD, Guido Ferrari, MD, David C. Montefiori, PhD, Xiaoying Shen, PhD, Sheetal Sawant, MPH, Nicole Yates, PhD, John Hural, PhD, Abby Isaacs, MS, Sanjay Phogat, PhD, Carlos A. DiazGranados, MD, Carter Lee, MBA, Faruk Sinangil, PhD, Nelson L. Michael, MD, Merlin L. Robb, MD, James G. Kublin, MD, Peter B. Gilbert, PhD, M. Juliana McElrath, MD, PhD, Georgia D. Tomaras, PhD and Lawrence Corey, MD.

About Fred Hutchinson Cancer Research Center:

At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the NIAID-funded HIV Vaccine Trials Network.

Media relations:

Aziel Gangerdine

HVTN: Director of Communications

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