NIH and Johnson & Johnson to Begin HIV Vaccine Trials on Humans

The U.S. National Institutes of Health (NIH) has announced that it will launch its Phase 3 Human Immunodeficiency Virus (HIV) efficacy trial on humans at 55 clinical research sites in the United States, Mexico, South America and Europe. The trial, called HPX3002/HVTN 706 or Mosaico, will assess whether or not the experimental HIV vaccine designed to trigger an immune response against a range of HIV strains can safely and effectively prevent HIV among men who have sex with men and transgendered individuals.^{1 2 3}

Mosaico, the third HIV vaccine trial in progress globally, is sponsored by Janssen Vaccines & Prevention BV, which is part of Janssen Pharmaceutical Companies of Johnson & Johnson. NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Army Medical Research and Development Command (USAMRDC) also funded the trial. Researchers at the HIV Vaccine Trials Network (HVTN) located at the Fred Hutchsinson Cancer Research Center in Seattle, Washington will be conducting the study.¹

The Bill and Melinda Gates Foundation also partners with U.S. federal agencies to fund HIV/AIDS vaccine development and clinical trials. ⁴

According to an NIH news release, Phase 3 of the clinical trial will involve 3,800 men and transgendered individuals who are HIV negative between the ages of 18 and 60 who have sex with men and/or transgender people. The study is expected to launch for open enrollment in August 2019. The reason this specific population is chosen as the sample for the study is because men who have sex with men and transgender people are disproportionately affected by HIV in the United States and Europe. In the United States, homosexual and bisexual men account for two thirds of new HIV cases despite representing only four percent of the total U.S. population.¹

All participants will be given a comprehensive HIV prevention package, including access to pre-exposure prophylaxis (antiretroviral drugs to reduce risk of contracting HIV). Participants will randomly be given either the experimental vaccine or a placebo. The experimental vaccine is made up four doses of Ad26.Mos4.HIV, a vaccine that uses an engineered common-cold virus that is believed not to cause illness (adenovirus serotype 26) to deliver four mosaic immunogens. The doses will be given four times over a one-year period. The last two doses will be given together with a bivalent (two-component) HIV envelope protein formulation.¹

Historically, there have been major challenges to developing a vaccine to prevent HIV, a viral infection that has been associated with the development of Acquired Immune Deficiency Syndrome (AIDS). Not only does the diversity of HIV strains pose a problem to creating a vaccine but also reservoirs of the virus can accumulate within certain cells and go undetected by the immune system. According to news reports, Johnson & Johnson’s experimental HIV vaccine has provided protection against HIV infection in nearly two-thirds of tested animals.⁵

Bruce Walker, director of the Ragon Institute, which is affiliated with Harvard University and Massachusetts Institute of Technology and focuses on immune approaches to disease stated, “It’s measurably better in animal studies than other vaccines tested thus far.” He adds, “The real questions are: Will it be protective? What percentage of people will be protected? And what will be the durability of the protection?”⁵

Another HIV Vaccine Containing An Attenuated Virus Nears Clinical Trials

In addition to the Mosaico trial, there is another HIV vaccine candidate that has been developed at the Oregon Health and Sciences University and licensed by Vir Biotechnology in California with funding from the Bill & Melinda Gates Foundation, which is almost ready to move on to clinical trials in humans.⁶ A study published in July 2019 describes an experimental vaccine that uses a live attenuated (weakened) form of the common herpes virus cytomegalovirus (CMV) for production.⁷ The original non-attenuated vaccine could not be used in humans as CMV can cause serious infections in humans, particularly in pregnant women or those with weakened immune systems.⁸

The new live attenuated HIV vaccine has shown to eliminate simian immunodeficiency virus (SIV), which is the monkey virus that causes symptoms in monkeys similar to symptoms of HIV in humans, in 59 percent of vaccinated rhesus macaque monkeys. These results are said to be similar to findings from earlier studies using the vaccine’s original non-attenuated version. The immunity generated by the attenuated vaccine is considered to be long lasting since nine of 12 vaccinated monkeys could still fight off SIV infection three years later.⁷

According to Klaus Früh, PhD, a co-author of the study, “This research, using rhesus CMV, provides potentially important insights into the design of a human CMV-based HIV vaccine.” He adds, “We significantly attenuated CMV and still got the same type of immune responses as with the wild version of this vaccine.”⁷

Another co-author Louis Picker, MD, states, “These papers are important because they recapitulate the previously reported unique CMV vector efficacy with a genetically modified vector that is highly attenuated and therefore potentially safer for clinical use.”⁸

Safety Concerns Using Live Attenuated Vaccines

Theoretically, live attenuated vaccines (LAV), including for smallpox, polio (OPV), measles, mumps, rubella, influenza, rotavirus, varicella and herpes zoster are considered to be safe since the live virus is weakened. Vaccinologists maintain that live attenuated viral vaccines elicit stronger and longer lasting immune responses than inactivated vaccines, even though the attenuation process is unpredictable and, sometimes, the attenuated vaccine strain viruses revert to a virulent form.⁹

According to a report published in Nature Biotechnology:

In the present regulatory environment the use of LAVs has also been limited by safety concerns, including reversion to wild-type virulence. Because LAVs are shed from vaccinees, they sometimes present a risk to unvaccinated individuals with impaired immunity.

There have been many cases of vaccine strain infection and transmission reported in the medical literature. ^{10 11 12 13} U.S. federal health agencies and the World Health Organization have placed a high priority on developing an HIV/AIDS vaccine that will be used in the U.S. and globally to, as stated on the NIH website, “realize a durable end to the HIV pandemic.”¹⁴