The CoronaVac vaccine against Covid-19, produced by Chinese pharmaceutical firm SinoVac, has been approved for use in 39 countries around the world—with more than 1 billion doses already distributed. Yet, following a series of Covid-19 deaths among Indonesian healthcare workers that were fully vaccinated with SinoVac, Malaysia will stop using the vaccine, and some have called for Thailand to do the same. So the question is:
Why are countries rejecting SinoVac?
This blog will help you to go through the scientific literature to give you everything you need to know about SinoVac’s effectiveness. Specifically, It will help you to know what is known about:
- How effective SinoVac is at preventing infection, hospitalization, and death?
- How the effectiveness changes against variants, such as gamma or delta?
- How quickly immunity drops after vaccination?
- How SinoVac compares to other vaccines?
And, as a bonus, here you will find a study that actually ranks vaccines for their effectiveness. Before looking at literature let's know:
What kind of vaccine is SinoVac? Is it like other Covid vaccines?
SinoVac’s CoronaVac vaccine is an inactivated virus. This is the most conventional type of vaccine, using the same technology as the polio vaccine in the 1950s.
Essentially, live SARS-CoV-2 virus was collected from infected patients in China at the beginning of the outbreak. Then, the virus was mass produced in monkey kidney cells, extracted, then treated with chemicals to inactivate it, rendering the virus unable to reproduce.
This is different from almost all other Covid vaccines, including the mRNA vaccines from Pfizer and Moderna, as well as the viral vector vaccines from Astra Zeneca, Sputnik, and Johnson & Johnson, which all stimulate the in vivo production of viral spike proteins. Only Sinopharm and the Indian Bharat vaccines use the inactivated virus approach that is found in SinoVac.
So, does it work? & How is vaccine effectiveness actually measured?
Vaccine effectiveness cannot be determined from observed trends, like for example, if infections or hospitalizations drop in a city or country once a vaccine is administered in the population. That trend tells us nothing about the vaccine. This is because there is no way to isolate what factor caused that decline to occur—it may have been the vaccine, or it may have been several other factors unrelated to the vaccine.
Instead, a study design needs to be able to measure both an outcome and a factor in each individual. The outcome is usually infection or hospitalization or death, and the factor would be whether that person has had a vaccine. The most reliable way to do this is with Phase 3 clinical trials—a type of study called a randomized placebo-controlled trial, where participants are randomly assigned into vaccine or placebo groups.
However, effectiveness can also be determined outside of trials using real-world data through two other study types: retrospective test-negative case-control studies and prospective cohort studies. We’ll be looking at data on SinoVac from all three of these study designs.
So, let’s get into it.
SinoVac had Phase 3 trials registered in Brazil, Chile, Indonesia, and Turkey. However, only data out of Turkey was used in the phase 3 trial publication, which came out in The Lancet on July 8, 2021.
The analysis included 10,029 participants, with 2/3 assigned to the vaccine and 1/3 assigned to a placebo. The results found that the vaccine was 83.5% effective at preventing symptomatic infection among fully vaccinated people. This number places it in the middle of vaccines for effectiveness based on phase 3 trial data alone.
So, SinoVac reports a relatively high vaccine effectiveness from this phase 3 trial, but it’s based on a fairly narrow set of data.
For a clearer answer, we need to look at studies with more data.
A much better study comes out of Chile. It’s a cohort study, which means it looked at an entire population of people in this case, every adult in the national public health insurance program of Chile, which ultimately included data on 10.2 million people covering 3 months from February 2nd to May 1st, 2021.
In that time, more than 4 million people received a SinoVac vaccine. And, overall, more than 218,000 people in the cohort got Covid-19, resulting in over 22,000 hospitalizations and 4000 deaths.
So with this much richer dataset, what did they find?
Among people fully vaccinated with SinoVac, they estimate the vaccine was:
- 65.9% effective for preventing Covid-19,
- 87.5% effective for preventing hospitalization, and
- 86.3% effective for preventing death from Covid.
So, with a much larger dataset we see that SinoVac’s actual vaccine effectiveness is probably about 66% for preventing symptomatic illness—a much lower number than the 83% reported from its published phase 3 trial.
But could any of these difference be due to differences in variants?
Other vaccines, including AstraZeneca and Pfizer, have reduced effectiveness among the variants alpha, beta, gamma, and delta. However, no such study has directly compared the effectiveness of SinoVac among different variants as of August.
What we can do, however, is look at genomic sequencing data to see what variants were spreading throughout each study. For example, the phase 3 study in Turkey covered the period from September 2020 to March 2021.
Looking at genomic sequencing data out of Turkey, we see that D614G was circulating. This form of the virus predates Alpha, Beta, and all other variants and is close to the original wild-type virus out of Wuhan.
On the other hand, the cohort study from Chile took place from February to May 2021. There, Lambda and Gamma were widely circulating. Using this information, we can see that variants may partly explain differences in the effectiveness estimates seen between Turkey and Chile. And, one more study out of Brazil shows how SinoVac did against Gamma.
In the study, which looked at the elderly in Sao Paolo, effectiveness of SinoVac against Gamma was:
- 46.8% for infection,
- 55.5% for hospitalization, and
- 61.2% against death.
What we see is that SinoVac’s effectiveness against all outcomes drops with older age and with more virus mutations.
But what about Delta?
Researchers in Thailand collected blood samples from healthcare workers who had been fully vaccinated with SinoVac and then tested to see if antibodies in that blood could neutralize the virus, looking at the original viral strain, known as wild-type, and also with the variants alpha, beta, and delta. What they found was that antibodies from people vaccinated with SinoVac were very good at neutralizing wild-type SARS-CoV-2—able to do it about 98% of the time.
This makes sense, since SinoVac is just an inactivated form of the wild-type virus. However, against alpha and beta, that neutralization rate dropped to 75 and 70%. Against, Delta, SinoVac antibodies could only neutralize the virus 48% of the time. So, SinoVac’s effectiveness is reduced against the current variants.
But what about waning immunity in our bodies over time?
We know already that immunity requires time to develop. Even after receiving a full vaccine dose, the full immune response generally develops about two weeks later.
But, what about after that? Once immunity does develop, how long does it last?
Researchers in both Brazil and China have shown that SinoVac’s antibody levels drop quickly. In Brazil, researchers looked at 133 healthcare workers that received two full doses of SinoVac and collected blood samples from them starting on the day of the first dose, then again at days 10, 20, 40, 60, and 110 days after the first dose. Then they measured levels of antibodies against SARS-CoV-2 proteins. After the first dose, virtually no antibodies developed. Then, about two weeks after the second dose, so 40 days after the first dose, antibodies peaked. Then, they steadily dropped. Antibody levels dropped in half about every 1 to 2 months. Even data from SinoVac itself confirms this drop. They found that after 6 months only 18% of people had neutralizing antibody levels considered sufficient for protection.
Now, the immune system has other tools beyond neutralizing antibodies, so this doesn’t mean a person’s immune system is completely helpless 6 months after vaccination with SinoVac. But, a major study in the journal ''Nature'' shows that neutralizing antibody levels are highly predictive of immune protection.
So with that in mind, let’s rank the vaccines. Looking strictly at phase 3 trial data, SinoVac might appear to be somewhere in the middle of the pack among Covid vaccines.
So who’s number one?
According to the study, Moderna is the most effective Covid vaccine. Next is Novavax. Third is Pfizer. And fourth is Sputnik. Then, we start to drop down to the next tier of vaccines. At 5 we have Astra Zeneca. Behind that is Johnson & Johnson. And, coming in last is SinoVac.
So, what does all this mean?
Because SinoVac has the lowest levels of neutralizing antibodies among widely used Covid vaccines, it is not an effective tool for creating herd immunity or preventing the spread of the coronavirus. That said, a SinoVac vaccine is still better than no vaccine when it comes to reducing risk of death and severe disease—at least for a short window of time.
However, compared to other Covid vaccines, SinoVac and its cousin Sinopharm, are less effective at preventing death, especially against current variants like Delta. Thus, the logical policy would be to seek better alternatives—just like Malaysia has already done.
However, experience thus far has shown that decisions to approve vaccines seem to be motivated more by geopolitical and financial interests, rather than on scientific data. Therefore, it’s up to citizens to keep pressure on their government officials to ensure transparency in vaccine agreements. One tool is the UNICEF vaccine market dashboard, which can be used to track vaccine agreements across the world.
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