This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

The COVID-19 pandemic sweeping across the globe has claimed more than 660,000 lives worldwide as of July 30, nearly a quarter of them in the United States.

Stemming the crisis will require a safe and effective vaccine, and scientists at Harvard Medical School and Beth Israel Deaconess Medical Center have been hard at work to develop one since the early days of the pandemic.

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Now, a research team led by Dan Barouch, an immunologist at HMS and Beth Israel Deaconess, has taken a critical step on that quest.

The team reports that a leading candidate COVID-19 vaccine developed by Barouch’s team in collaboration with Johnson & Johnson triggered the development of neutralizing antibodies against SARS-CoV-2, the virus that causes COVID-19, and led to robust protection against infection in nonhuman primates.

An early version of the new study’s manuscript was published July 30 in Nature, and builds on the team’s previous research that appeared in Science earlier this year. The manuscript has been accepted for publication in Nature.

“We are encouraged by our findings and hope that this vaccine works in humans,” said Barouch, the William Bosworth Castle Professor of Medicine at HMS and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess. “The vaccine led to robust protection against SARS-CoV-2 in rhesus macaques and is now being evaluated in humans.”

The vaccine uses an inactivated, harmless form of a common cold virus, called adenovirus serotype 26 (Ad26), to deliver the SARS-CoV-2 spike protein into host cells, where it stimulates the body to raise immune responses against the coronavirus.

Barouch has been working on the development of a COVID-19 vaccine since January, when Chinese scientists released the SARS-CoV-2 genome. Barouch’s group, in collaboration with Johnson & Johnson, developed a series of vaccine candidates designed to express different variants of the SARS-CoV-2 spike protein, which is the major target for neutralizing antibodies.

In the current research, conducted in 52 rhesus macaques, Barouch and colleagues gave 32 adult animals a single dose of one of seven different versions of the Ad26-based vaccine. The remaining 20 animals received sham vaccines as placebo controls. All vaccinated animals developed neutralizing antibodies following immunization. Six weeks after immunization, all animals were exposed to SARS-CoV-2. All 20 animals that received the sham vaccine became infected and showed high levels of virus in their lungs and nasal swabs. Of the six animals that received the optimal vaccine candidate, Ad26.COV2.S, none showed virus in their lungs, and only one animal showed low levels of virus in nasal swabs. 

Moreover, the levels of neutralizing antibodies correlated with the degree of protection, suggesting that this biomarker will be useful in the clinical development of COVID-19 vaccines for use in humans.

“Our data show that a single immunization with Ad26.COV2.S robustly protected rhesus macaques against SARS-CoV-2 challenge,” said Barouch, who is also a member of the Ragon Institute of MGH, MIT, and Harvard, and a co-leader of the vaccine working group of the Massachusetts Consortium on Pathogen Readiness.

A single-shot immunization has practical and logistical advantages over a two-shot regimen for global deployment and pandemic control, but a two-shot vaccine will likely be more immunogenic, and thus both regimens are being evaluated in clinical trials, Barouch added.

“We look forward to the results of the clinical trials that will determine the safety and immunogenicity, and ultimately the efficacy, of the Ad26.COV2.S vaccine in humans,” he said. 

Investigators at Beth Israel Deaconess and other institutions have initiated a first-in-human phase 1/2 clinical trial of the Ad26.COV2.S vaccine in healthy volunteers. Kathryn E. Stephenson is the principal investigator for the trial at Beth Israel Deaconess, which is funded by Janssen Vaccines & Prevention B.V., a pharmaceutical research arm of Johnson & Johnson. 

Pending clinical trial outcomes, the Ad26.COV2.S vaccine is on track to start a phase 3 efficacy trial in 30,000 participants in September.

For full list of co-authors and collaborators, please see the full-text report in Nature.

The authors declare no competing financial interests. Barouch, Zahn, Wegmann, Rutten, Bos, Manen, Vellinga, Custers, Langedijk, Kwaks and Schuitemaker are co-inventors on related vaccine patents. Zahn, Wegmann, Rutten, Bos, Manen, Vellinga, Custers, Langedijk, Kwaks, Stoffels, Mammen, Van Hoof and Schuitemaker are employees of Janssen Vaccines & Prevention B.V. and hold stock in Johnson & Johnson.

This project was funded in part by the U.S. Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA) under contract HHS0100201700018C.  We also acknowledge support from Janssen Vaccines & Prevention B.V., the Ragon Institute of MGH, MIT and Harvard, the Mark and Lisa Schwartz Foundation, the Massachusetts Consortium on Pathogen Readiness (MassCPR) and the National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603 to D.H.B.; AI007151 and AI152296 to D.R.M.; AI146779 to A.G.S.; 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197 to R.S.B.).  We also acknowledge a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award to D.R.M.

Adapted from a Beth Israel Deaconess news release.