CoronaVac, the coronavirus vaccine developed by China, is one of the most advanced vaccines. In anticipation of the initial announcements about the ongoing Phase III clinical trials, the results of Phases I and II have just been published in The Lancet. CoronaVac is based on a historically proven approach: the live attenuated vaccine.
China has been working intensively on a coronavirus vaccine since this spring. While Pfizer, Russia, and Moderna announced the efficacy of their vaccines in the press, the Chinese laboratory Sinovac, which already markets three vaccines, against Hepatitis A, Hepatitis B, and Influenza, is also making progress.
Evidently, Sinovac did not wait for the results of Phases I and II to be published in The Lancet but continued to the next phase. Phase III started in September, particularly in Turkey and Brazil. However, the trials had to be interrupted due to an unexpected serious event that took place in October among the participants of the Butantan Institute in Brazil. On November 11, the Brazilian health authorities approved the resumption of the trials.
The CoronaVac vaccine is based on the same principle as the first vaccines in history, namely live attenuated vaccines, which consist of injecting a weakened version of SARS-CoV-2 to stimulate the immune system. Pasteur used this method to develop his rabies vaccine. The BCG vaccine, which protects against tuberculosis bacteria (Bacille de Calmette et Guérin), is also a live attenuated vaccine. These vaccines are highly immunogenic and provide long-term protection, so they are sometimes not recommended for immunocompromised patients, such as AIDS patients. However, this has yet to be confirmed in the specific case of CoronaVac.
A randomized, double-blind clinical trial
The results published in The Lancet Infectious Disease cover both Phases I and Phase II clinical trials. The tests are the same except that Phase II is being conducted on a larger number of people. In this case, about 20 for Phase I in each group compared to about 100 for Phase II. A total of 743 people between the ages of 18 and 59 who have never been infected with SARS-CoV-2 were used. Scientists are therefore interested in vaccine-induced seroconversion, i.e. the occurrence of specific SARS-CoV-2 antibodies in these previously seronegative individuals.
Two doses of vaccine have been tested: 3 and 6 µg of attenuated virus in 0.5 milliliters of aluminum hydroxide. A first group received a dose on day 0 and day 14, a second group on day 0 and day 28. Each person is randomly assigned to a group and neither doctors nor patients know the content of the shots (double-blind). Finally, the results are compared with a placebo group.
At the end of this vaccination protocol, scientists examined for each group and each dose not only the seroconversion but also the tolerability, i.e. the occurrence of side effects after injection.
A well-tolerated and effective vaccine
In general, vaccination was well tolerated. The most common side effects were pain in 20-25% of participants, followed by discomfort at the injection site in 25-30% of participants, regardless of the dose injected.
Regarding the occurrence of antibodies, scientists looked into two parameters: neutralizing antibodies and the antibodies that are specific to the RBD of the S protein of SARS-Cov-2 14 and 28 days after the second dose. In the 100 people who participated in phase 2, the vaccination produced neutralizing antibodies in more than 90% of them.
Doing one injection on Day 1 and then a second injection on Day 28 with the concentrated vaccine of 6 µg is the most effective formula to stimulate the production of antibodies: neutralizing and anti-RBD IgG antibodies were observed in 100% of the people in this group.
These clinical trials did not focus on cellular immune response (T cell activation), but this will be investigated in Phase III. It is not possible to estimate the effectiveness of CoronaVac at this time, so we have to wait for the first conclusions of the third phase of clinical trials.