Strategy pursued in developing Ebola vaccine could be used to produce COVID-19 vaccine

In animal testing, experimental Ebola vaccine based on platform developed by US pharmaceutical company in partnership with Brazilian researchers conferred immunity against hemorrhagic virus with single dose.

By Elton Alisson  |  Agência FAPESP – The strategy used to develop a candidate vaccine against Ebola by US pharmaceutical company Flow Pharma in partnership with Brazilian researchers could also direct the development of a vaccine against SARS-CoV-2, the coronavirus that causes COVID-19.

In tests with mice, a single dose of the experimental Ebola vaccine proved capable of conferring immunity against the virus that caused a severe outbreak of Ebola hemorrhagic fever in West Africa in 2013-16. 

The results of the tests in animals were reported in late February 2020 on bioRxiv, an open-access preprint repository for the biological sciences.

“A similar approach to the method used to develop this Ebola vaccine could be followed to produce a SARS-CoV-2 vaccine,” Edécio Cunha Neto, one of the authors of the platform, told Agência FAPESP. Cunha Neto is a professor at the Heart Institute (INCOR), part of the University of São Paulo’s Medical School (FM-USP).

Daniela Santoro Rosa, a professor at the Federal University of São Paulo (UNIFESP), is also participating in the project.

“Daniela and I are the authors of the search for the sequence for an Ebola vaccine,” said Cunha Neto, a co-principal investigator for the Institute for Research in Immunology, hosted at INCOR and one of the National Science and Technology Institutes (INCTs) funded by FAPESP in the state of São Paulo in partnership with the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government.

The Ebola vaccine comprises fragments of peptides from the virus encapsulated in micrometric particles. The purpose of the peptides is to stimulate the recipient’s immune system to produce a potentially protective response.

The researchers used computer algorithms to identify regions of the Ebola virus that contain promising peptides for use as antigens in a vaccine. 

One of the criteria for the algorithms to locate these potential regions in the viral structure was that they had to be very well conserved, with little variation between one isolate and another to ensure the vaccine’s efficacy even against variants of the pathogen.
Another criterion was that the immune system in most people must be capable of recognizing the regions selected. “This is very important to ensure that the vaccine’s coverage is as comprehensive as possible, since these regions of the viral genome will be basically the same in all Ebola viruses wherever they’re circulating, and the vaccine will induce an immune response in most people,” Cunha Neto explained. 

Prospective peptides located in the best conserved regions of the virus were tested in cells from 30 patients who survived the 2013-16 Ebola outbreak in the Democratic Republic of Congo (formerly called Zaire).

The results showed that immune system cells called CD8+ T lymphocytes from 26 of these 30 patients responded to the peptide NP44-52. An experimental vaccine was therefore produced with NP44-52 encapsulated in microspheres as a biodegradable dry powder, which remained stable at room temperature.

The experimental vaccine was given to genetically modified mice (C57BL/6) used as a model for human diseases, and was found to produce a protective immune response 14 days after a single dose was administered.

According to the article, the platform developed by the researchers can be deployed for fast-track production and delivery of a peptide vaccine in response to a new viral threat.

COVID-19 vaccine

The same approach could be applied to COVID-19, the authors argue, since the novel coronavirus also has conserved regions, and prospective peptides for the development of a candidate vaccine can be identified.

If researchers act now during the COVID-19 pandemic, blood samples can be collected and analyzed so as to create a database of optimal candidate peptides for inclusion in a vaccine with potentially broad coverage for subsequent rapid manufacture and deployment, they stress. 

Cunha Neto is also pursuing another strategy for a COVID-19 vaccine under development at INCOR’s Immunology Laboratory with FAPESP’s support.

“The US pharmaceutical company had the idea of using the Ebola candidate vaccine approach to develop a COVID-19 vaccine. We continue to collaborate with them on other projects. The strategy we prefer for the development of a vaccine here in Brazil is somewhat different,” he said.

He noted, however, that as stressed by some of the world’s leading experts on vaccines including Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID) in the United States, it will take 12 to 18 months to develop and test a reliable COVID-19 vaccine. Animal testing and clinical trials in humans are required to ensure the vaccine is safe and effective, he explained.

The article “An effective CTL peptide vaccine for Ebola Zaire based on survivors’ CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design” (doi.org/10.1101/2020.02.25.963546) by C.V. Herst, S. Burkholz, J. Sidney, A. Sette, P.E. Harris, S. Massey, T. Brasel, E. Cunha Neto, D.S. Rosa, W.C.H. Chao, R. Carback, T. Hodge, L. Wang, S. Ciotlos, P. Lloyd and R. Rubsamen can be read at: www.biorxiv.org/content/10.1101/2020.02.25.963546v2.abstract. 

The article “Coronavirus infections – more than just the common cold” (10.1001/jama.2020.0757) by Catharine I. Paules, Hilary D. Marston and Anthony S. Fauci can be read in the Journal of the American Medical Association (JAMA) at jamanetwork.com/journals/jama/fullarticle/2759815.