Which vaccines work best for which variants?
Dr. Edsel Maurice T. Salvana
As the Philippines surpasses five million vaccine doses administered, the rate of vaccination continues to accelerate and there is real progress in rolling back the pandemic. Countries that have vaccinated a significant portion of their population are beginning to open up and are starting to recover a semblance of normalcy. As more brands of vaccines are rolled out, confidence that all the current vaccines protect against severe disease is at an all time high. Data on substantial transmission blocking effects from a multitude of vaccines are also beginning to come in.
How have the last few months changed the outlook for the future? Is there really a chance that we can restart school this year, and let the children and the seniors out very soon? What needs to happen to bring this about sooner? We review recently available data from four of the earliest vaccines with widespread rollouts, namely Pfizer, Moderna, Sinovac, and Astra.
For preventing disease and death, vaccines performed as well or better in real life compared with clinical trials.
The high vaccine efficacy rates in clinical trials for the mRNA vaccines (Moderna and Pfizer) were pretty much confirmed with real world rollouts. Vaccine efficacy refers to how well a vaccine protects the vaccinee in clinical trials, while vaccine effectiveness is the protection seen in real world conditions. Real-world data from Israel on its Pfizer vaccination showed 95.3 percent effectiveness against any SARS-CoV-2 infection, 97.5 percent protection against severe or critical hospitalization, and 96.7 percent decreased risk for death from the disease. A prospective study among healthcare workers in the US vaccinated with either Pfizer of Moderna showed an overall vaccine effectiveness of 90 percent against RT-PCR confirmed SARS-CoV-2 illness, including asymptomatic infections.
Astra and Sinovac, which had mediocre vaccine efficacy numbers in their clinical trials, have outperformed vaccine effectiveness expectations. Many scientists feel that limitations in the methodologies from some of the clinical trials may have led to low vaccine efficacy. In the case of Sinovac, a short interval between doses (two weeks between doses in the Brazil trials) and a highly exposed healthcare worker population may have contributed to less-than-optimal efficacy numbers. Suboptimal dosing intervals for Astra may also have contributed to lower initial efficacy numbers.
Astra has now been shown to be more effective when the second dose is given at 12 weeks compared with earlier than six weeks. The effectiveness for the first dose is as high as 80 percent, and a second dose increases this to 85 to 90 percent. Sinovac, in real-world experience in 10 million people in Chile, showed a vaccine effectiveness against moderate to severe disease of 85 percent. In a recent trial in Indonesia among 128,290 healthcare workers, Sinovac prevented symptomatic disease in 94 percent of participants, prevented hospitalization in 96 percent, and prevented death in 98 percent. These real-world numbers are just as good as those for the mRNA vaccines.
In other words, all four vaccines: Pfizer, Moderna, Sinovac, and Astra have shown similar real- world effectiveness against symptomatic disease. This is important because effectiveness is a more realistic measure of how well a vaccine works since it accounts for logistics and handling issues. All four vaccines prevent symptomatic disease in the 85 to 95 percent range, and all are nearly 100 percent effective in decreasing the risk of dying. Data from other vaccines continues to be gathered, but there is a reasonable expectation that efficacy against symptomatic and severe disease will remain high.
Vaccines work against the variants
More and more studies are showing that all the available vaccines remain highly effective against severe disease for many of the variants of concern. The mRNA vaccines have been shown to retain significant activity against B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.2 (India) variants. Sinovac has shown good activity against P.1 and is being studied for the rest of the variants of concern. Astra has decreased activity for symptomatic B.1.351 (South Africa) but continues to protect against severe disease. It also still works against B.1.1.7 and has slightly less efficacy against P.1.
Other vaccines are being studied for efficacy against the variants of concern, but it is unlikely that any of the current variants will completely escape from any of the vaccines that have emergency use authority. Boosters covering the specific variants of concern have been developed and are currently undergoing clinical trials.
Vaccines that block transmission
The most exciting aspect of vaccine effectiveness is the ability to block transmission. While early clinical trials correctly focused on clinical efficacy, transmission-blocking properties will allow for a faster exit from the pandemic and potentially lead to herd immunity.
The prospective mRNA vaccine trials in healthcare workers in the US showed a 90 percent decreased risk of infection, which also included asymptomatic infection. Asymptomatic infection is the most difficult to detect and control, and vaccines that decrease the risk of both asymptomatic and symptomatic infections will have a profound effect on overall transmission. Pfizer data from Israel showed a reduction in asymptomatic infections by 91.5 percent. It also showed substantial decreases in viral load in those with breakthrough infections. Decreased viral load means decreased infectivity. Limited data on Astra showed a decrease of 50 percent to 67 percent in infections among recipients, including asymptomatic ones. None of these studies, however, measured actual transmission rates within the community, and so the data just tell us that vaccinated individuals are less likely to transmit infection. They don’t answer the question of what impact this has on unvaccinated individuals.
In the most ambitious and comprehensive transmission-blocking study to date, the Brazilian town of Serrana vaccinated over 95 percent of its inhabitants with Sinovac and began tracking transmissions and infections to show how well Sinovac decreases transmission in the community. Similar trials are under way in other countries with other vaccines. Interim results from Serrana are already showing a marked reduction in cases, deaths, positivity rate, and healthcare utilization. The primary analysis is due this May and while tracking will continue for over a year, there should be good data very soon.
The newest findings from real-world studies confirm that at the very least, the four vaccines that have been discussed—Astra, Sinovac, Moderna, and Pfizer—all work very well against preventing symptomatic and severe COVID-19 infection. They most likely work against all the variants in preventing severe disease, and they all are transmission-blocking to a certain extent. More data means more confidence in opening up the economy, and reclaiming the ability to safely meet, travel, and be physically close to friends and family. Vaccines indeed work, and they are the keys to freedom.