The development of a safe and effective vaccine will likely be required to end the COVID-19 pandemic. A group of scientists, led by Beth Israel Deaconess Medical Centre (BIDMC) immunologist Dr Dan H Barouch, now report that a leading candidate COVID-19 vaccine developed at BIDMC in collaboration with Johnson & Johnson raised neutralising antibodies and robustly protected non-human primates (NHPs) against SARS-CoV-2, the virus that causes COVID-19. This study builds on the team's previous results.
"This vaccine led to robust protection against SARS-CoV-2 in rhesus macaques and is now being evaluated in humans," said Barouch, who is director of BIDMC's Centre for Virology and Vaccine Research.
The vaccine uses 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 neutralising antibodies.
Barouch and colleagues conducted a study in 52 NHPs, immunising 32 adult rhesus macaques with a single dose of one of seven different versions of the Ad26-based vaccine, and giving 20 animals sham vaccines as placebo controls. All vaccinated animals developed neutralising antibodies following immunisation. Six weeks after the immunisation, 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, neutralising antibody responses correlated with 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 immunisation with Ad26.COV2.S robustly protected rhesus macaques against SARS-CoV-2 challenge," said Barouch, who is also the William Bosworth Castle professor of medicine at Harvard Medical School, 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 immunisation 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. 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."
Investigators at Beth Israel Deaconess Medical Centre (BIDMC) and other institutions have initiated a first-in-human Phase 1/2 clinical trial of the Ad26.COV2.S vaccine in healthy volunteers.
Dr Kathryn E Stephenson, is the principal investigator for the trial at BIDMC, which is funded by Janssen Vaccines & Prevention, BV, 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.
Abstract
A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in nonhuman primates. Fifty-two rhesus macaques were immunized with Ad26 vectors encoding S variants or sham control and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs following SARS-CoV-2 challenge. Vaccine-elicited neutralizing antibody titres correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in nonhuman primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.
Authors
Noe B Mercado, Roland Zahn, Frank Wegmann, Carolin Loos, Abishek Chandrashekar, Jingyou Yu, Jinyan Liu, Lauren Peter, Katherine McMahan, Lisa H Tostanoski, Xuan He, David R Martinez, Lucy Rutten, Rinke Bos, Danielle van Manen, Jort Vellinga, Jerome Custers, Johannes P Langedijk, Ted Kwaks, Mark JG Bakkers, David Zuijdgeest, Sietske K Rosendahl Huber, Caroline Atyeo, Stephanie Fischinger, John S Burke, Jared Feldman, Blake M Hauser, Timothy M Caradonna, Esther A Bondzie, Gabriel Dagotto, Makda S Gebre, Emily Hoffman, Catherine Jacob-Dolan, Marinela Kirilova, Zhenfeng Li, Zijin Lin, Shant H Mahrokhian, Lori F Maxfield, Felix Nampanya, Ramya Nityanandam, Joseph P Nkolola, Shivani Patel, John D Ventura, Kaylee Verrington, Huahua Wan, Laurent Pessaint, Alex Van Ry, Kelvin Blade, Amanda Strasbaugh, Mehtap Cabus, Renita Brown, Anthony Cook, Serge Zouantchangadou, Elyse Teow, Hanne Andersen, Mark G Lewis, Yongfei Cai, Bing Chen, Aaron G Schmidt, R Keith Reeves, Ralph S Baric, Douglas A Lauffenburger, Galit Alter, Paul Stoffels, Mathai Mammen, Johan Van Hoof, Hanneke Schuitemaker, Dan H Barouch
[link url="https://www.bidmc.org/about-bidmc/news/2020/07/covid-19-vaccine-protects-non-human-primates"]Beth Israel Deaconess Medical Centre material[/link]
[link url="https://www.nature.com/articles/s41586-020-2607-z"]Nature abstract[/link]