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News | Jan. 19, 2023

U.S. Military HIV Research Lends Lessons Learned to COVID-19, HIV

By Claudia Sanchez-Bustamante, MHS Communications Walter Reed Army Institute of Research

The U.S. military has led HIV research since 1986, when it stood up the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research at a time when reports of AIDS diagnoses showed almost twofold year-to-year increases in the United States.

Since then, MHRP has been at the forefront of the battle against HIV, helping to protect the U.S. military and improve global health through research to develop an HIV vaccine, reduce new infections, and advance strategies to induce long-term HIV remission.

In February 2020, the emergence of COVID-19 presented a new historic global public health challenge. Like HIV, it represented a destabilizing force that impacted the world, but existing HIV research data and lessons learned helped spearhead the development of COVID-19 vaccines at a “historic pace,” said U.S. Army Col. (Dr.) Julie Ake, director of the MHRP WRAIR, in Silver Spring, Maryland.

A Top Public Health Challenge Threatening Force Readiness

HIV is a “global destabilizing force impacting partner militaries and challenging public health in strategic geographies,” said Ake.

“HIV continues to threaten global health with 38 million people living with HIV worldwide and approximately 40 million deaths since 1981.”

And despite the development of prevention tools, there were 1.5 million new infections in 2020, as well as “several hundred new HIV infections in U.S. service members annually, which impairs military readiness, imposes a significant cost to military health systems, and threatens blood safety,” she added.

Military Advances in Medicine

Between 2003 and 2006, MHRP led the first-of-its-kind RV144 clinical trial, known as the Thai HIV Vaccine Study.

“It was the first clinical trial to show some efficacy in preventing HIV infection,” said Ake. “Study results showed that a preventive HIV vaccine is possible, and the landmark trial continues to provide scientific direction to help guide vaccine development and testing.”

She explained that the trial results, announced in 2009, paved the way for MHRP to conduct many experimental vaccine studies to help speed the discovery of a more effective vaccine.

“For example, we showed that longer intervals between the primary vaccination series and later doses boost improved immune responses,” she said.

The MHRP is now studying other ways to improve vaccine strength and breadth, she said, including:

  • Novel vaccine platforms
  • Fractional dosing, which involves using a fraction of the standard dose of a regular vaccine to reach more individuals or minimize the side effects of a full dose of vaccine
  • Adjuvants, which are ingredients that can help people receiving a vaccine create a stronger immune response

“This year, we began a Phase 1 trial [which involves testing in humans] in Bangkok, Thailand to evaluate two HIV vaccine candidates,” said Ake. “One is administered with and another without the Army's novel ALFQ  to evaluate adjuvants and boosting strategies for better immune responses. We also began a trial at the WRAIR Clinical Trials Center in Silver Spring to select the optimal dose of the ALFQ adjuvant to use with protein-based vaccines.”

Additionally, Ake said MHRP began its first preclinical animal study of an mRNA HIV vaccine in early 2022. (Preclinical research occurs prior to clinical studies with humans, to find out if a drug or treatment is likely to be useful.)

“The WRAIR’s pilot bioproduction facility is developing the capacity to manufacture mRNA-based HIV vaccines for clinical trials on campus and internationally,” she said. “We think that this technology, along with improved adjuvants, are important for the next generation of HIV vaccine candidates.”

The study is ongoing and expected to wrap up animal activities in early 2023.

Why has an HIV Vaccine Taken so Long?

A vaccine that prevents HIV acquisition with “more than modest efficacy” has not yet been developed, said U.S. Air Force Col. (Dr.) Jessica Cowden, chief of the Department of Retrovirology at the Armed Forces Research Institute of Medical Sciences, in Bangkok, Thailand.

“Much of that is due to the extreme complexity of the virus, its mechanisms of infection, and its pathogenesis, or the process by which disease develops,” said Cowden. “Other factors are related to the global genetic diversity, the lack of animal models, and the changing landscape of prevention strategies which make large efficacy trials increasingly more difficult.”

The virus has many different HIV subtypes and strains circulating around the globe, added Ake.

“Once a person is infected, HIV continues to mutate rapidly. It hides from the immune system, making it very hard to target with a single vaccine,” she said. “The types of immune responses needed for protection are complex, and we continue to improve the strategies to induce these immune responses.”

Lessons Learned from COVID-19 Research

The decades-long HIV research science provided valuable lessons for COVID-19 vaccine research.

It was “firmly built on the HIV vaccine research foundation and leveraged the scientific advances and capabilities of decades of HIV research,” said Cowden. It also leveraged extensive research network sites and community engagement teams and strategies, she added.

For example, “monoclonal antibodies were already under development to prevent and treat HIV when COVID-19 emerged,” said Ake.

In addition, experts from the HIV field—including Ake and others at WRAIR—provided technical assistance to federal efforts which came to be known as the Countermeasures Acceleration Group.

“WRAIR’s unique strengths in infectious diseases research, specifically around vaccine development, community engagement, clinical trial design, and immune monitoring laboratory assays, helped guide tremendous efforts to develop and test novel vaccines, diagnostics, and therapeutics,” she said.

For example, she said scientists at WRAIR leveraged expertise developed through the study of HIV and other viruses to design, produce, and test a type of vaccine candidate for COVID-19 called Spike Protein Ferritin Nanoparticle in animal and human trials.

“As the epidemic evolved, WRAIR also contributed knowledge about the ongoing genetic diversity of the virus and the potential impacts of virus variability on the vaccines in use and in development,” she added.

Cowden listed additional contributions of the HIV vaccine research effort to the COVID-19 vaccine development effort. These include:

  • The COVID-19 effort tested vaccine platforms that had already been developed and tested in HIV as well as for other emerging pathogens prior to SARS-CoV-2.
  • Expertise in viral diversity and evolution.
  • Expertise in structure-based vaccine design, immunology, and structural biology.
  • Leveraging global clinical research capacity sites.
  • Applying and utilizing community engagement, education, and participation experience pioneered in HIV research for COVID-19 research.
  • Research collaborations.

Ake explained that MHRP is part of several National Institutes of Health-funded networks, which the COVID-19 effort leveraged with other worldwide collaborators for coronavirus studies.

For example, “MHRP clinical research site partners in Kenya and Uganda played a key role in testing candidate vaccines and therapies, including enrolling over 2,000 participants in COVID vaccine efficacy trials,” she said. And “at the local level, community advisory boards—already in place for HIV vaccine studies—were leveraged for COVID studies to help engage communities.”

Unparalleled COVID-19 Vaccine Development

The success of the COVID-19 vaccine development has also provided valuable insight for HIV research. For example, Ake said work on the mRNA vaccine platform for HIV vaccines is being accelerated because of the success of the mRNA COVID-19 vaccines.

“The speed and global collaboration with which COVID-19 vaccines and treatments were tested and approved was unprecedented,” said Ake. “It shows what is possible,” and provides hope that timelines for HIV vaccine development will become quicker as well.

In addition, “the rapid testing and scalability of mRNA products seen through COVID-19 have increased the acceptability of such an intervention to both prevent and treat diseases,” said Ake, underscoring the importance of strong industry engagement.

Cowden highlighted that the COVID-19 vaccine development effort was “unparalleled in its resourcing,” in terms of human effort and financial investment. It united public, private, and academic entities across sectors to work towards a common purpose, she said.

“There are many lessons from this effort that people hope to harness and apply in the HIV vaccine development effort,” she added.

Some of those include:

  • Using technologies developed for COVID-19 for HIV vaccines.
  • Accelerating development timelines by modeling regulatory pathways from COVID vaccine development efforts (such as clinical development steps done in parallel to improve efficiency and sharing information processes between regulatory bodies).
  • Continuing to build on collaborations between academia, industry, and governments.
  • Harnessing creativity and unity of purpose and decision-making from COVID-19 vaccine development efforts and applying those back in the HIV vaccine development field.

Likewise, “the research community must continue to engage community leaders, key opinion leaders, and community organizations to try to build trust and ensure the concerns and needs of minority and higher risk populations are considered and included in clinical trial design and execution,” concluded Cowden.

For more information on HIV testing and treatments, talk to your health care provider.