Nasal drop vaccine candidate for coronavirus from India

Hyderabad-based biotechnology company Bharat Biotech International today announced that it has a potential intranasal vaccine for the novel coronavirus SARS-CoV-2 in the works. The company is hoping to begin human clinical trials later this year.

An international collaboration of virologists from the University of Wisconsin–Madison in the US, Wisconsin-based vaccine company FluGen Inc. and Bharat Biotech is pursuing the vaccine lead called 'CoroFlu'. Company sources told Nature India that they have begun the development and testing of the vaccine built on the backbone of FluGen's existing flu vaccine candidate M2SR.

M2SR is a self-limiting version of the influenza virus that induces an immune response against the flu. Based on an invention by UW–Madison virologists and FluGen co-founders Yoshihiro Kawaoka and Gabriele Neumann, ‘CoroFlu’ stands apart from other candidates since its principle has already been shown to be safe and well-tolerated in humans, in Phase I and Phase II clinical trials, Bharat Biotech said in a release.

Kawaoka’s lab will insert gene sequences from the novel coronavirus SARS-CoV-2 into M2SR so that the new vaccine also induces immunity against the coronavirus, said Bharat Biotech's business development head Raches Ella. The safety and efficacy in animal models will be tested at UW–Madison’s Influenza Research Institute.

“Bharat Biotech will manufacture the vaccine, conduct clinical trials, and prepare to produce almost 300 million doses of vaccine for global distribution," Ella was quoted as saying in the release.

FluGen will transfer its existing manufacturing processes to Bharat Biotech to scale up production of the vaccine for clinical trials. Bharat Biotech has commercialized 16 vaccines, including a vaccine developed against the H1N1 flu that caused the 2009 pandemic.

Company sources said refining the vaccine concept and testing in laboratory animal models at UW–Madison will take three to six months. Bharat Biotech will then scale up production for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by the fall of 2020, according to the release.

Phase I and Phase II clinical trials have shown the safety of the M2SR flu vaccine among "hundreds of subjects", according to the release. Besides, M2SR’s ability to induce a strong immune response, and the ability of influenza viruses to carry sequences of other viruses make M2SR an attractive vaccine option, the company said.

The release quoted Kawaoka lab's senior virologist and co-founder of FluGen Gabriele Neumann as saying, “We are going to modify M2SR by adding part of the coding region for the coronavirus spike protein that the virus uses to latch onto cells and begin infection.” CoroFlu will also express the influenza virus hemagglutinin protein, which is the major influenza virus antigen. "So we should get immune responses to both coronavirus and influenza,” she said.

Explaining the working principle of the vaccine candidate, FluGen co-founder, president and CEO Paul Radspinner said M2SR is a unique form of the flu virus. It lacks a gene called M2, which restricts the virus from undergoing only a single round of replication in cells. “The single replication means the virus can enter the cell, but it can’t leave,” he said in the release. “So, in essence it tricks the body into thinking it’s infected with flu, which triggers a full immune response. But since it can’t replicate further, you don’t get sick.”

CoroFlu, like M2SR, will be delivered through the nose. This route of administration mimics the natural route of infection by coronavirus and influenza and activates several modes of the immune system. Intranasal delivery is more effective at inducing multiple types of immune responses than the intramuscular shots that deliver most flu vaccines, the release says.

Commenting on the vaccine candidate, virologist and CEO of Wellcome Trust DBT India Alliance Shahid Jameel said, “Though the Flu M2R platform has not yet been tested for its efficacy to prevent flu, this is a very interesting lead. It may be a good opportunity for the vaccine candidate to be sped up towards approval.”

[Nature India's latest coverage on the novel coronavirus and COVID-19 pandemic here . More updates on the global crisis here .]