Sinovac: what we now know
With the arrival of the vaccine shipment today, the Philippines now has a total of 9,329,050 vaccine doses. @HerdImmunityPH (on Twitter) posted an infographic regarding the vaccine breakdown by brand:
It is undeniable that the Philippines is currently hinging its response primarily on Sinovac, with almost 70% of the available vaccines provided by the Chinese brand. Over a real-world effectiveness study done in Chile, Sinovac’s Coronavac had an efficacy of 65% against symptomatic disease, 87% against hospitalizations, and 86% against death. This was a study done over 10.2 million people, and the results have been quite promising.
Other studies that speak of its effectiveness include the Indonesian healthcare worker study, where >90% of the study’s members have been vaccinated with Sinovac. It was 94% protective against symptomatic infection, 96% from hospitalization, and 98% from death.
An important caveat, however, from the study was that the rates of immunization were significantly high: the high number is likely inflated because of it. According to Bloomberg, “[I]n the Indonesian health worker study, and another in a Brazilian town of 45,000 people called Serrana, nearly 100% of people studied were fully vaccinated, with serious illness and deaths dropping after they were inoculated.”
What’s more telling from this study and the Serrana study, which revealed 80% symptomatic protection against COVID-19, 86% protection against hospitalization, and 95% against death, is that a high number of people must be vaccinated for Coronavac to be fully effective. In Serrana, for instance, 95% of the adult population was vaccinated.
It’s definitely a great leap for Sinovac: a few months ago, I had been among the doubters with respect to its efficacy due to the lack of Phase III peer-reviewed trial results, and a lack of definitive evidence with respect to its effectiveness. That has changed: Sinovac is indeed an effective vaccine two weeks after two doses have been administered.
However, it must also not be denied that it is one that is inferior (in terms of evidence and study results) to the mRNA vaccines (Pfizer/Moderna) and AstraZeneca. For starters, Uruguay and Chile are among the countries that have been using Sinovac for a majority of its COVID-19 immunizations. Contrast this to the United Kingdom and Israel, which have predominantly utilized the mRNA vaccines (and AstraZeneca).
All four countries have high rates of vaccination. However, the difference is that Israel and United Kingdom use mRNA vaccines predominantly, in contrast to the utilization of Sinovac in Chile and Uruguay.
One of the likely reasons to this difference is the greater generation of neutralizing antibodies by the mRNA vaccines. There has been a pre-print noting that ONE dose of Pfizer/BNT generated the same amount of neutralizing antibodies as TWO doses of the Sinovac vaccine.
Another reason is that the much greater antibody titers generated by the mRNA vaccines may be more effective in preventing transmission: this study states that “our results suggest that mRNA-based vaccines do not only prevent SARS-CoV-2 infections among vaccinated individuals but lead to a substantial reduction in infections among unvaccinated household members.”
Prevention of transmission, of course, matters. Due to the lower amount of antibodies generated by Sinovac in contrast to Pfizer (image below), it is likely enough to prevent severe disease but not prevent transmission.
Another concern that the wide use of Sinovac is its significantly decreased effectiveness in the presence of the Gamma variant. In another pre-print, Sinovac was only 42% effective in the elderly during a Gamma-dominated epidemic. Alarmingly, it was only 18.6% effective prior to two weeks after the second dose, only rising to 42% once 14 or more days after the second dose have passed.
Also unlike Pfizer or AstraZeneca, Sinovac does not seem to provide any first-dose protection from COVID across multiple studies. In the Indonesian healthcare worker study, the first-dose effect of Sinovac was 13% protective against COVID-19; in the Chile study, it was 16%. Effectiveness only reaches the high percentage observed two weeks after the completion of the second dose.
Another consideration arising from the relatively lower effectiveness of Sinovac against the more uniform excellent results of mRNA vaccines is its waning efficacy. As time passes, the antibodies that the vaccines provide wanes, and it’s heavily reliant (per Khoury, et. al) on initial efficacy.
This has led people to talk about boosters especially with respect to Sinovac, and it will be a question that has to be answered by the Philippine government eventually.
One of the most important messages that it could impart with respect to immunization is that being fully vaccinated is not an excuse not to follow the minimum health care protocols. If the vaccine is Sinovac, the first-dose is barely protective, and non-essential travel must be avoided as much as possible. Until and unless 75% of the Philippine population become immunized, there must be no loosening of the minimum health protocols, especially with the rise of the Alpha and Delta variants.
At this time, there have been no studies yet on Sinovac’s efficacy with respect to both variants. However, Pfizer and AstraZeneca through UK’s Public Health England have shown to be effective against both variants (with AstraZeneca being 60% and Pfizer being 87% effective).
Another important message to impart is that for Sinovac, two doses of the vaccine must be administered for it to be effective. It is barely more than placebo with just one, and it is imperative that two doses must be obtained. Even two doses might not be enough. Why?
It was mentioned in a previous paragraph that Sinovac generates fewer neutralizing antibodies than Pfizer or AstraZeneca. When it is exposed to variants, efficacy shifts further to the left (Sinovac becomes less effective) because the variants have already modifications in their conformation that decrease the antibodies from binding to the virus. It was clearly evidenced that Sinovac’s effectiveness was significantly affected by the Gamma variant, and presumably, Alpha and Delta also have effects on viral neutralization.
Because Sinovac is the most regularly supplied vaccine for the Philippines, the DOST endeavor to mix-and-match Sinovac with the other available doses will hopefully come to fruition soon. Studies that have previously used a Pfizer booster to an initial AstraZeneca dose have produced extremely positive results, even addressing AZ’s ineffectiveness against the Beta variant! Hopefully the same will occur with Sinovac as the first dose and Pfizer or an mRNA vaccine as its booster: that will certainly expand the number of people that will be better protected against COVID and utilize the Sinovac supplies at the same time.
SUMMARY
In summary, Sinovac has gone a long way in showing itself as an effective vaccine. However:
- The first dose of Sinovac has little protective effect, so there must be strict adherence to the minimum health care protocols even after the first jab.
- Full protection occurs two weeks after the second dose of Sinovac, and not before. Because, however, Sinovac has not been shown to curb transmission, double masks and physical distancing remain important.
- Boosters are likely an earlier necessity with Sinovac, especially with its effectiveness compared to the mRNA vaccines.
- In a highly-vaccinated population, Sinovac offers even more protection against symptomatic COVID, hospitalization, and death.
- A mix-and-match approach with Pfizer may increase Sinovac’s antibody generation and effectiveness.
Pfizer and AstraZeneca are better overall vaccines against COVID-19 than Sinovac. However, Sinovac has the least amount of allergic reactions and may be safely given to the immunocompromised. It definitely has a niche, but I believe that in light of the high levels of vaccine hesitancy, better policy would be to use transmission-hindering vaccines in the cosmopolitan cities to minimize transmission. Like Singapore, Sinovac will be an option to the hyperallergenic individuals or individuals who could not tolerate the mRNA vaccines. With more studies, hopefully Sinovac can be paired with an mRNA vaccine to maximize what is available to us.
