Two candidate vaccines show promise in protecting monkeys against COVID-19

Embargoed until: Publicly released:
Peer-reviewed: This work was reviewed and scrutinised by relevant independent experts.

Randomised controlled trial: Subjects are randomly assigned to a test group, which receives the treatment, or a control group, which commonly receives a placebo. In 'blind' trials, participants do not know which group they are in; in ‘double blind’ trials, the experimenters do not know either. Blinding trials helps removes bias.

Animals: This is a study based on research on whole animals.

Two candidate COVID vaccines have shown they can help protect monkeys exposed to SARS-CoV-2, the virus that causes COVID-19. The first vaccine, being trialled by Johnson and Johnson, is a single-dose vaccine made from an adenovirus - a type of common cold virus. It was able to offer partial or full protection against SARS-CoV-2 infection in the respiratory tract, an effect thought to be required to prevent transmission and disease in humans. The second vaccine, also based on an adenovirus and known as the Oxford vaccine, was shown to reduce viral load in fluid from the lungs of monkeys, and no pneumonia was observed in vaccinated animals. However, there was no difference in nasal shedding of the virus between vaccinated and control (unvaccinated) animals.

Journal/conference: Nature

DOI: 10.1038/s41586-020-2607-z

Organisation/s: Harvard Medical School, USA, National Institute of Allergy and Infectious Diseases, USA

Funder: Paper-1 This project was funded in part by the Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA) under contract HHS0100201700018C. We also acknowledge support from Janssen Vaccines & Prevention BV, the Ragon Institute of MGH, MIT, and Harvard, Mark and Lisa Schwartz Foundation, 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. Paper 2 - This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) (1ZIAAI001179-01) and the Department of Health and Social Care using UK Aid funding managed by the NIHR.

Media release

From: Springer Nature

Paper 1: Single-dose vaccine protects against SARS-CoV-2 in nonhuman primates

A single dose of a vaccine made from an adenovirus protects rhesus macaques against SARS-CoV-2, reports a paper in Nature. The optimal version of the vaccine is currently being evaluated in clinical trials.

A safe and effective vaccine for SARS-CoV-2 has become a global priority. Vector-based vaccines use viruses to express fragments of the target pathogen to stimulate an immune response. Adenoviruses, a group of viruses that are linked to illnesses such as the mild cold, are effective at invading human cells. Vaccines based on adenovirus serotype 26 (Ad26) have been shown to induce immune responses to various pathogens in both nonhuman primates and humans.

Dan Barouch and colleagues developed a series of Ad26 vectors encoding different variants of the SARS-CoV-2 spike protein and present results from tests in 52 adult rhesus macaques. The authors show that these vaccines elicit an immune response. In addition, the vaccines offer partial or full protection against SARS-CoV-2 infection in the respiratory tract, an effect thought to be required to prevent transmission and disease in humans. The best-performing vaccine, Ad26-S.PP (given the vaccine name Ad26.COV2.S), has now entered clinical trials.

The authors note that robust responses were achieved after a single dose. A single-shot SARS-CoV-2 vaccine would have practical advantages over a multiple-dose vaccine. However, the authors expect that a two-dose regimen with the Ad26-S.PP vaccine would produce a stronger immune response.

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Paper 2: ChAdOx1 nCoV-19 vaccine protects macaques against COVID-19-related lung damage

The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2, which is currently undergoing human clinical trials in the UK, elicits an immune response and reduces the viral load in macaques exposed to SARS-CoV-2, reports a paper published in Nature. The vaccine was found to protect the macaques from COVID-19 pneumonia – a complication of SARS-CoV-2 infection in which the lungs become inflamed and may fill with fluid. Preliminary results from this research were used to facilitate the start of clinical trials of the vaccine in humans.

ChAdOx1 nCoV-19 is made from a weakened chimpanzee adenovirus (a group of viruses that can cause a range of illnesses, including the common cold) that expresses the SARS-CoV-2 spike protein (a structure that enables the coronavirus to enter human cells). Vincent Munster and colleagues report the efficacy of this vaccine against SARS-CoV-2 in rhesus macaques. They show that a single dose of ChAdOx1 nCoV-19, given to six macaques 28 days before exposure to SARS-CoV-2, is effective in preventing damage to lungs and drastically reduces the viral load (when compared with six control animals). A further six macaques were given a booster course of two doses of the vaccine, at 56 and 28 days before challenge, which increased the immune response. The vaccinated animals showed no evidence of immune-enhanced inflammatory disease, which has been observed in some preclinical studies of vaccines against SARS-CoV.

The authors note that there was no difference in viral shedding from the nose between vaccinated and control animals. This finding indicates that ChAdOx1 nCoV-19 may not prevent infection or transmission, but may reduce illness. The study has led to clinical trials of the ChAdOx1 nCov-19 vaccine, which have enrolled more than 8,000 volunteers as of the beginning of July 2020.

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