Not available in Canada: A look at COVID-19 vaccine tech from China, India and Cuba

COVID-19 vaccines developed in China are already being used in several countries around the world. And some developed in India, Kazakhstan and Cuba have been in use domestically for their own populations even before completion of Phase 3 trials.

Vaccines being made in some of those countries (including the Serum Institute of India's Covishield version of the AstraZeneca vaccine) use the viral vector technology or mRNA technologies used to inoculate Canadians. But other vaccines developed domesticallyare quite different.

Here's a closer look at two kinds of COVID-19 vaccines inactivated and conjugate protein vaccines developed in middle-income countries and not available in Canada.

Inactivated Vaccines

Who's making these: Vaccines of this kind have been developed by Sinovac (CoronaVac), headquartered in Shanghai China and Sinopharm (BBIBP-CorV), in Beijing, China, Bharat Biotech (Covaxin) in Hydrabad, India and The Research Institute for Biological Safety Problems (QazVac) in Zhambyl, Kazakhstan.

How they work: This is atried and true strategyused in many vaccines against diseasesincluding hepatitis A and rabies. It involves growing up whole viruses in this case, SARS-CoV-2, the virus that causes COVID-19 and then inactivating them so they can't cause infection. For SARS-Cov-2, the inactivationis typically done with a chemical called beta-propiolactone. The virus is injected with an adjuvant, typically aluminum-based, to boost immune response. Unlike mRNA vaccines, these vaccines also don't require ultra-cold storage. A regular fridge will do.

What stage are they at? The frontrunners are the Chinese inactivated vaccines,already approved for emergency use and being used in mass vaccination in dozens of countries around the world on nearly all continents. They were being evaluated by the World Health Organization for Emergency Use Listing this spring. Bharat Biotch released interim Phase 3 results for its Covaxin vaccine in March and April, and the vaccine has been in use in its home country since January, when it was approved for emergency use there. Similarly, the Research Institute for Biological Safety Problems rolled out its vaccine QazVac on April 23, about halfway through the completion of its Phase 3 trials.

How good are they? None have released final results of their Phase 3 trials, but all results so far surpass the World Health Organization's minimum of 50 per cent efficacy:

• Sinovac's vaccine efficacy varied from 50.4 per cent in Brazil to 91.25 per cent in Turkey. However, the way the trials were run and what populations were included were highly variable. For example, unlike othertrials for different kinds of vaccines that tested only volunteers with symptoms for COVID-19, the Brazil trial tested volunteers without obvious symptoms.

• Sinopharm has said its vaccine has a 79 per cent efficacy, and the U.A.E. said its trials of the vaccine showed it had 86 per cent efficacy.

• Bharat Biotech has reported interim efficacy as 79 to 81 per cent.

Colin Funk, an adjunct professor withQueen's University in Kingston, Ont., and biomedical consultant with Vancouver-based Novateur Ventures co-authored a paper in the journal Viruses earlier this year comparing all the frontrunning vaccines around the world, including Sinovac's and Sinopharm's.

"They are working, but not as well for sure as the mRNA vaccines," he said. Pfizer and Moderna both reported efficacy of more than 94 per cent. Funk said it's been difficult to get reliable information as the Chinese companies haven't published their final results. Since they're in use in many countries, though, he added that it should become clear in a few months how well they work.

While officially these vaccines' efficacy is lower, they do have anadvantage fewer side effects, especially fever. That's the side effect which can cause the most concern, said Craig LaFerriere, head of vaccine development at Novateur Ventures, who co-authored the paper with Funk. Fever appear in less than two per cent of those vaccinated with inactivated vaccines, compared to 15 per cent of those who receive mRNA and viral vector vaccines.

Conjugate vaccines

Who's making these: There are at least two Cuban vaccines of this type, billed as the only COVID-19 vaccines of their kind:Soberana 02 (the name means "sovereignty"),made by the Finlay Institute of Vaccines in Havana; and Mambisa, developed by the Center for Genetic Engineering and Biotechnology (CIGB).

How they work: Conjugate protein vaccines are a special type of protein subunit vaccine made with an antigen (a substance that can cause an immune response) from the target disease bound to a strong antigen from another disease to boost the immune response. A common one that you have probably been vaccinated with is Haemophilus influenza type b (Hib), a standard childhood vaccine against meningitis, which includes the sugar coating or polysaccharide from Hib linked to a diphtheria, meningococcal or tetanus protein. In the case of Soberana 02, the receptor binding domain from the spike protein of the SARS-CoV-2 virus that causes COVID-19 is bound to a tetanus toxoid, Cuban doctors reported in global healthcare journalBMJ . A second Cuban conjugate vaccine, Mambisa, contains the same coronavirus protein and a Hepatitis B protein. Protein-based vaccines can be stored in a regular fridge.

What stage are they at? Soberana 02 is one of two Cuban vaccines listed by the World Health Organization as being in late-stage Phase 3 clinical trials right now (The other is Abdala a traditional protein subunit vaccine with an aluminum-based adjuvant). It's already being used in Havana as part of an "interventional study," that doesn't involve double-blind testing or placebos. Mambisa, designed to be administered as a nasal spray instead of an injection, started Phase 1 trials in March.

How good are they? We don't know. Data from the trials have not been released or published, although there are some preclinical results published on a preprint server. Vicente Vrez Bencomo, director-general of the Finlay Institute told the journal Nature in April that Phase 1 and 2 trials of Soberana 02 showed 80 per cent of people who received two doses had an antibody response. Some were given an additional booster in the form of Soberana Plus, a version of the vaccine targeted at those who have previously had COVID-19 and 100 per cent of them showed an antibody response, he added.

But Cuba has successfully made a Hib vaccine based on this technology, and has decades of experience with it, said Helen Yaffe, a lecturer in economic and social history at the University of Glasgow who has studied Cuba's state-owned biotechnology industry. "I think most of the world takes Cuba's biotech products very seriously," she said. Funk of Queen's University agreed that Cuba does very good research, and said of Soberana 02, "For sure I think that would be a candidate that might advance and could be used in certain countries around the world," Funk said. "We'll just have to see."