A Chinese firm, known as Sinovac, one of the leading COVID-19 vaccine developer contenders, recently revealed results from a peer-reviewed paper in the medical journal The Lancet. Collected from its first Phase 1 and Phase 2 clinical trials investigating the inactivated vaccine known as CoronaVac, these first studies sought to demonstrate the safety and immunogenicity of CoronaVac: that is, the experimental vaccine sponsor’s testing of the product’s ability to trigger an immune response, as well as the monitoring of any side-effects, including adverse events. The study sponsor clinical trial design incorporated a couple of different dosages and inoculation schedules. This class of vaccine, inactivated, represents more of a traditional approach when compared to the more technologically novel messenger RNA-based vaccine candidates developed by Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b3). Currently, there is no approved mRNA-based vaccine; however, Pfizer just filed for an emergency use authorization (EUA) with the U.S. Food and Drug Administration (FDA) based on the existing results thus far. The results evidence some benefits but, overall, are considered inferior to the two leading Western vaccine candidates.
The CoronaVac study (NCT04352608) involved a randomized, double-blinded, and placebo-controlled Phase 1 and 2 study of the SARS-CoV-2 inactivated vaccine produced by Sinovac. The main objective of this early-stage effort was to evaluate the safety and immunogenicity of the experimental vaccine in healthy adults aged 18 to 50 years old. This study was led by Principal investigator Fengcai Zhu, a physician with the Jiangsu Provincial Center for Disease Control and Prevention.
Designed to test safety and immunogenicity, the study team uncovered that, in fact, CoronaVac does trigger antibody immune response; however, they disclosed at a lower level than those found in other individuals who have already recovered from SARS-CoV-2 infection. The results of the CoronaVac Phase 1 and 2 study are inferior to the findings thus far for the leading “Western” candidates, including Pfizer/BioNTech (U.S. and Germany) and Moderna (U.S.), as they have shown that antibody immune response is at least as high as individuals who have recovered from SARS-CoV-2 infection or even higher than those ranges reported the Washington Post.
NPR reported a quote from Dr. Gregory Poland, a vaccinologist and professor at the Mayo Clinic in Rochester, MN, who declared, “I’d be concerned…that seemed to induce lower antibody levels than what we’ve seen with other vaccines and lower than what you see in most people who have had disease and recovered.”
Phase 3 Clinical Trials
Sinovac has had a difficult time launching studies in China, due to the low number of COVID-19 infections in that country, despite the fact that the pandemic started there in Wuhan. Rather, the publicly-traded firm has had to compete against other Chinese firms (SinoPharm and CanSino Biologics), as well as against Russia’s Sputnik V for Phase 3 clinical trials host countries: Sinovac has been able to secure deals for Phase 3 studies in Turkey, Brazil and Indonesia. While Sinopharm has secured other host countries for pivotal trials.
TrialSite observes a possible trend that the Chinese and Russian vaccine makers may be targeting lower to middle-income countries (LMICs) while Western vaccine producers ( Moderna, Pfizer/BioNTech, AstraZeneca, Johnson & Johnson, Novavax, Curevac, etc.) may first and foremost target the wealthiest nations with deeper pockets for higher quality products.
Inactivated vaccines such as CoronaVac are relatively economical and expedient to produce when compared to the more novel mRNA-based investigational products from Pfizer/BioNTech and Moderna, for example. Hence, there could be some market force drivers that pull these vaccines to certain parts of the world.
Emergency Use Questioned
It’s important to remind that CoronaVac has been pushed out for actual emergency use by China as early as June, as has been reported by TrialSite and prominent publications such as the Washington Post.
This raised serious eyebrows, as the actual CoronaVac Phase 1/2 clinical trial only commenced by April, so only a couple of months went by before the extremely early stage experimental candidate was already used on the general population deemed at high risk. This form of activity raised a number of ethical considerations. Other Chinese vaccine companies had similar opportunities, as did the Russian Sputnik V, which actually declared the vaccine candidate “registered” and hence approved by regulatory authorities in that nation, despite no Phase 3 trials and an uncomfortably condensed Phase 1 and 2 study.
Fengcai Zhu, a physician with the Jiangsu Provincial Center for Disease Control and Prevention