Q: Could you explain more about the vaccines being used in developing countries? Are these countries getting inferior vaccines?
A. For a long time, very little was known about many of the vaccines in wide use outside the U.S., especially the ones from China like CoronaVac, Sinopharm, and CanSino, and the vaccine from Russia, Sputnik V. But more studies have been recently published to give us better insight into their safety and efficacy.
➡️How do these vaccines work?
Sputnik V (from the Gamaleya Research Institute in Russia) and Convidecia (from the Chinese company, CanSino Biologics) are non-replicating viral vector vaccines. Both use a modified adenovirus to deliver instructions to our cells to produce the spike protein of SARS-CoV-2 and temporarily display it outside the cell. This triggers our immune system to begin producing antibodies to SARS-CoV-2. The technology is similar to the one used by Oxford/AstraZeneca and J&J, but Sputnik V requires 2-doses (like Oxford/AstraZeneca), whereas Convidecia (CanSino) is intended as a 1-dose vaccine (like J & J).
CoronaVac (from the Chinese company, Sinovac) and the vaccine from Sinopharm both use inactivated SARS-CoV-2 virus. These vaccines are made by growing the virus that causes COVID-19 in a lab and then killing it. When injected, the vaccine exposes the body’s immune system to the inactivated virus without risking a serious disease response. The CoronaVac and Sinopharm vaccines use a more “traditional” method that’s been used for decades in other vaccines like polio and rabies. Both the CoronaVac and Sinopharm vaccines require 2 doses.
All these vaccines have great benefit in low-resource settings because of their low cost, and because they can be stored in a standard freezer (Sputnik V) or refrigerator (the vaccines from China).
➡️How safe and effective are these vaccines?
Based on the results of a Phase 3 clinical trial published in Feb 2021, there were 16 confirmed COVID-19 cases in the vaccine group, and 62 confirmed cases in the placebo group for an efficacy of 91.6%. There were 20 severe COVID-19 cases – all in the placebo group. No serious side effects were linked to the vaccine in the trial.
More recently, Russian scientists announced the results of a “real world” study based on 3.8 million people in Russia demonstrating an efficacy of 97.6% (results not published yet).
It is unknown how long immunity lasts with this vaccine, and the trials did not study how well the vaccine performs against variants. But in a pre-print that was posted online this month, researchers studied the antibody responses to the B.1.1.7 and B.1.351 variants in subjects receiving the vaccine. They showed that 67% of the samples failed to neutralize the B.1.351 variant, but did efficiently neutralize the B.1.1.7 variant.
Based on a pre-print describing a Phase 3 clinical trial in Brazil:
14 days after the second dose, there were 85 COVID-19 cases in the vaccine group and 168 COVID-19 cases in the placebo group, for an efficacy of 50.7% against symptomatic COVID-19. But it also had an efficacy of 83.7% against cases requiring medical treatment, and an efficacy of 100% against severe disease (all 6 cases of severe COVID-19 were in the placebo group). There were 67 serious adverse events reported but none were related to vaccination.
The company also announced that analyses of Phase 3 trials in Turkey and Indonesia showed an efficacy of 65.3% and 91.3%, respectively, against symptomatic infection, though it’s unclear why estimates differed so much. These results have not been published yet.
In the first real-world study of this vaccine in Chile (10.5 million people), CoronaVac was 67% effective in preventing symptomatic infection, 85% effective in preventing hospitalizations and 80% effective in preventing deaths – 14 days after the second dose. However, after only one dose, the vaccine prevented just 16% of symptomatic infections, 35% of hospitalizations and 40% of deaths – emphasizing a critical need to administer BOTH doses (study not yet published).
Phase 3 trial results have not been published, but trials are ongoing. In Dec 2020, the company announced that an interim analysis of its Phase 3 trial showed an efficacy of 79%. Meanwhile, the United Arab Emirates (UAE) announced that the vaccine had an efficacy of 86% against COVID-19 infection, and 100% efficacy in preventing moderate and severe cases, based on an interim analyses of its Phase 3 trial (results not published).
In March 2021, the UAE started testing a third dose of Sinopharm in people who did not generate an antibody response after two shots.
Phase 3 trial results have not been published, though trials are ongoing in several countries including Pakistan, Russia, Mexico, Chile, and Saudi Arabia. In Feb 2021, Pakistan’s health adviser announced that CanSino had an efficacy of 65.7% at preventing symptomatic cases, and an efficacy of 90.98% in preventing severe disease, based on an analysis from the Phase 3 trial in that country (results not published).
➡️ What’s the controversy with these vaccines?
A vaccine needs have at least 50% efficacy to be approved for use by the world’s leading drug regulators and the WHO. All the vaccines appear to clear this threshold though to varying degrees.
However, one of the sources of controversy is that many countries approved these vaccines for use BEFORE results from Phase 3 trials were available (and in some cases, before these trials were even begun), and before other scientists could independently evaluate the safety and efficacy data. Phase 3 trials are necessary to evaluate the safety and efficacy of vaccines at the population level and in different groups of people. Traditionally, and in most parts of the world, vaccines are not administered until the analyses of Phase 3 trial data are conducted, even for vaccines authorized for emergency use. But many countries approved the vaccines from China and Russia before Phase 3 data analyses were completed, contributing to widespread hesitancy in many countries.
The good news is that Phase 3 trial results for some of these vaccines are finally being published, showing safety and efficacy estimates that are compatible with WHO requirements. And while there’s some concern that the efficacy estimates for some of these vaccines are not as high as other vaccines approved for use, Gao Fu, the director of the Chinese Center for Disease Control and Prevention, suggested that other strategies may be tested and implemented, like increasing the number of doses administered, or mixing vaccines that use different technologies.
In an ideal world, all countries would have full access to vaccines with the highest levels of safety and efficacy. Unfortunately, many of the vaccines administered in high-income countries have not been available to low- and middle-income countries due to cost, availability, and storage requirements. Unless efforts are devoted to addressing these barriers, much of the world will need to rely on a more diverse portfolio of vaccines to stem the global surge in COVID-19 cases. The good news is that the vaccines in use in many developing countries appear to help with preventing severe disease and hospitalization – which is critical to prevent the collapse of healthcare systems with limited resources to begin with.