In race to get COVID-19 vaccine, are we setting the bar low?

COVID-19 vaccine bandwagon

It isn't Hester alone that has jumped onto the COVID-19 vaccine bandwagon, according to government more than 30 vaccines are currently in various stages of development in India and a few are expected to hit human trials next few months.

The list of companies developing vaccines include the traditional powerhouses of vaccine making such as Serum Institute of India, Bharat Biotech, Biological E, Zydus Cadila, Indian Immunologicals; there are other small biotechs such as Gurgaon-based Premas Biotech, Pune-based Gennova Biopharmaceuticals and Aurbindo Pharma's subsidiary Auro Vaccines.

Even a diagnostic lab called Neuberg Supratech Reference Laboratory is also working on a vaccine. There are many other COVID-19 vaccine projects that are underway but not publicly announced yet. The companies are developing vaccines based on live virus, protein sub units of virus, RNA and DNA.

Some of the companies are doing the vaccine development internally, while others have collaborated with foreign biotech companies and academic institutions.

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India has reported about 52,987 COVID-19 confirmed cases and 1,785 deaths. Globally, there are 3.8 million COVID-19 cases, and 2.65 lakh people have died. Many countries have imposed lockdowns at a huge economic cost to contain the spread of virus. Vaccine is considered to be sure shot panacea against the pandemic. Vaccination helps to quickly establish herd immunity against the disease, and allows countries to get back to normal.

History says that the fastest time it took to develop a vaccine is five years, but it usually takes double that time to bring vaccine from lab to market.

With Indian drug regulator assuring speedy permissions for clinical trials, waiver of data requirement for animal studies and approval of manufacturing licenses within seven days, Indian companies believe that a vaccine could be possible anywhere between nine months to two years. The average timeline that's widely cited is 12-18 months. That's an unprecedented timeline to develop a vaccine.

To achieve the fete, companies will have to shorten the vaccine development life-cycle, that comes with possible risks of omissions and commissions in terms of safety and efficacy of the vaccine.

Fast-tracking development
"I am little nervous on 12-18 months timeline, it is long enough in the context of a pandemic, but extremely tight time-frame to develop a vaccine," said an executive of a vaccine company who didn't want to be named. His company is one of the major vaccine makers of India.

"We can guarantee immediate safety of the vaccine, which means nothing is going to happen to a person who is taking it, like fever and other allergic reactions. Also we can ensure acceptable efficacy of the vaccine. But the grey area is the long term safety and efficacy. What happens to a person if he is infected with the virus one year or two years down the line. How will that person immune system react, will the vaccine gives the desired protection, we need time to determine these things," the above mentioned executive said.

Also Read | COVID-19 vaccine hunt heats up globally, still no guarantee

There have been high profile cases of companies coming up short. The recent example is the Dengue vaccine of Sanofi.

Setting bar low

Conventionally a vaccine aims at more than 90 percent effectiveness, but now even if the vaccine achieve 60-70 percent, regulatory agencies are ready to back them.

They cite example of flu vaccine, which is approved even though its effectiveness is less than 50 percent.

"Given the emergency pandemic situation, governments are ready to push the bar for efficacy lower, that makes things easy," the above executive said.

Animal model challenges

A pre-clinical study that involves testing the vaccine on animals is very crucial before a vaccine enters human trials.

The fate of many vaccine candidates will be determined in the pre-clinical stage itself. This study has to be robust and takes upto six months. Here too some vaccine makers are rushing without having a animal trial data.

Also Read | Sanofi to enroll thousands for its coronavirus vaccine trials

The race to make a vaccine is also compounded by the problem of availability of animal disease model or animal challenge model

Mice, the mainstay of animal studies however is inert to SAR-CoV-2 virus. So researchers have to engineer a mice (transgenic) that expresses both the mouse and the human versions of the receptor's gene ACE2. ACE2 receptors provide gateway for the virus to enter the cell.

"There are a few companies that offer these mice (disease) models, they are based in US, France and Japan. They give preference to vaccine developers in their countries, and it is also quite expensive," the above quoted vaccine executive said. The mice model market is billion dollar market.

Also Read | COVID-19 might never have a vaccine, just like HIV and dengue: Experts

Despite the absence of animal challenge model, vaccine makers are still moving ahead.

"It is a human virus. Having a mouse model is very difficult. Earlier it took many years to develop challenge (disease) model. It is equally rare that a human virus will co-infect a mouse. What we are testing in the pre-clinical is that is not a challenge model. We will take the candidate and see the antibody response. We will also how see the toxicity to the animal," said Dr Prabuddha Kundu, co-founder & Managing Director of Premas Biotech.

Meanwhile World Health Organisation (WHO) is working with several laboratories across the world to provide R&D blueprint of the animal models available to vaccine developers. Monkeys and ferrets are now found to be infectable with SARS-CoV-2, show evidence of virus replication and shed virus in nasal swabs. But a vailability of these animals for testing would be another challenge.

Human trials, funding, scale-up and distribution

The department of biotechnology in India will be facilitating and overseeing human trials. But with multiple vaccine trials to commence shortly, there is a dilemma among vaccine developers on how to enrol patients.

Many would be conducting clinical trials on humans for the first time and doesn't have necessary expertise.

Indian government is funding vaccine projects in the initial phase of development through BIRAC grants. Once these vaccine projects advance into larger human trials they would be require huge funding to set up manufacturing, scaling it up and distribution.

For instance Serum estimated the cost of the project at Rs 300 crore. Serum indicated that it is may look at securing outside funding. Executives say its possible to do a vaccine at much lesser cost than Serum.

Indian vaccine companies themselves rely on funding from government, WHO, Coalition for Epidemic Preparedness Innovations (CEPI) and non-profits like Bill and Melinda Gates Foundation, to fund vaccine development projects and de-risk the costs of investment.

But even after funding clinical trial costs and setting up manufacturing facilities, company's aren't sure they would get a payback.

Indian companies learned hard, when they jumped to develop vaccines against H1N1 influenza outbreak in 2009 but soon realised that there isn't much demand for the vaccine.

The US government model is something that can be considered. The New York Times reported that US administration has identified 14 vaccine projects it intends to focus on. It would further narrow the group to a handful that could go on, with government financial help and accelerated regulatory review.

"One can create a splash in media by announcing COVID-19 vaccine project, but how many will be able to sustain, is what we need to watch out for," the above executive said.

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