February 6, 2021

expert reaction to announcement of results of phase III of Sinovac vaccine in China

Sinovac have announced the phase III results of its COVID-19 vaccine.

Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:

“Sinovac has published a press release reporting the results of phase III trials of CoronaVac, its COVID-19 vaccine. This is a more conventional vaccine than the mRNA and vector vaccines currently in use in the UK: it uses “killed” SARS-CoV-2 virus as the antigen. As such, it may contain a wider range of antigens, not just the spike glycoprotein, which might – in theory, at least – mean better cross-protection against virus variants. I am not aware if this has been tested so far. It seems possible to me that, because the injection contains the antigens themselves, rather than the genetic template from which our cells create the spike glycoprotein antigen, it might work faster (no delay while the antigen is built by the ribosomes); but this is, again, speculation on my part. 

The trials – conducted in Brazil, Turkey, Indonesia, and Chile – used a different dosing regime from that used for the trials of the Moderna, Pfizer-BioNTech, and AstraZeneca vaccines, with an earlier booster dose – at only 14 days. The rationale for choosing a 14-day prime-boost interval is not explained. We know that most vaccines are more effective with a longer prime-boost interval, so it is possible that this 14-day interval will not be the optimal interval; but there doesn’t appear to be any data on this. 

I am a little confused by the findings as presented in the press release. It appears to describe overall findings from Brazil and Turkey – presumably combining data from both countries; and then goes into more detail on the data from Turkey. As far as I can tell, no data is presented from the trials in Indonesia or Chile. 

It appears that participants were observed for 14 days from the second dose of vaccine – there appears to be no information in the efficacy of a single dose. It is likely that immunity will continue to improve after 14 days from the second dose, so the results may underestimate the efficacy after this time. 

The – presumably combined – results, it says were:

“As of December 16, 2020, there were 12,396 health workers over 18 years old enrolled. A total of 253 positive cases were collected during the observation period. After 14 days following vaccination with 2 doses of vaccine following a 0, 14 day schedule, the efficacy rate against diseases caused by COVID-19 was 50.65% for all cases, 83.70% for cases requiring medical treatment, and 100.00% for hospitalized, severe, and fatal cases.”

This is consistent with the results from other vaccine trials, with increasing efficacy against increasingly severe disease. The participants in this trial were all healthcare workers (HCWs) over the age of 18. 

Participants’ ages are not reported here, but the subsequent reporting says that the HCWs in Turkey were all below the age of 60. Particularly given the concerns expressed by eg France, Germany, and Switzerland about the relative lack of evidence of efficacy in the highest risk, older population, this is problematic.

The press release goes on to report on two stages of the trial in Turkey. It is not clear if these are subsets of the data reported previously, or separate, except that the second stage included “the general population” (not just HCWs). It states:

“There are two stages of the phase III clinical trial in Turkey. Participants comprised health care workers in the first stage (K-1) and the general population in the second stage (K-2), with all participants ranging from 18 to 59 years old. As of December 23, 2020, there were 918 participants enrolled in K-1 and 6,453 participants in K-2, for a total of 7,371 participants. Among them, 1,322 participants completed the two-dose vaccination and entered the 14-day observation period after receiving the second dose of the vaccination. Based on an analysis of 29 cases, the efficacy rate for COVID-19 prevention was 91.25% after 14 days following the two-dose vaccination, in adherence with the 0, 14 day schedule.”

Note the age range: “all participants ranging from 18 to 59 years old” and my previous comments. 

This paragraph doesn’t go into detail about the outcomes. There is no breakdown by severity.

In common with other products, these phase III trials provide no information on whether the vaccine will prevent “Long Covid”. 

The results are of data collected by 16 Dec 2020, so probably don’t give an indication of whether the vaccine will be effective against variants of the virus. I am not sure how easy it will be for this technology to be “tweaked” to cover such variants.

No information is provided as to whether study participants were routinely tested for asymptomatic or paucisymptomatic infections, so we cannot make any preliminary deductions about the vaccine’s likely efficacy in preventing infection and transmission (although this is generally beyond the scope of phase III trials). 

In summary, according to the limited information in this press release, the Sinovac vaccine appears to be at least 80% effective at preventing disease requiring medical treatment, and over 90% effective at preventing hospital admission and death in vaccine recipients ages 18 to 59.

The short prime-boost interval may not be optimal. It may (quite reasonably) have been chosen in order to provide earlier results: there is such an urgent need to prevent serious illness that this may have been appropriate. 

I shall be interested to see if efficacy will be improved when study participants have been followed up for longer, or if a greater prime-boost interval is used.

And I hope that results in older recipients will soon be available, as these are the groups at greatest risk of severe disease or death.”

http://www.sinovac.com/?optionid=754&auto_id=922

Declared interests

Dr Peter English: “none to declare.”