CLINICAL MATTERS
As more and more people are vaccinated against Covid-19, the positive effects of immunization are emerging. While there is still little data on the ability of the vaccines to prevent transmission, more and more vaccines are showing excellent clinical efficacy. Clinical efficacy is defined as the ability to prevent symptomatic disease, but not necessarily asymptomatic disease. More important, almost all the vaccines for which some phase 3 data have been released show very strong protection against the development of severe disease.
More vaccine platforms proven to work
Listed below are the different vaccines and their clinical efficacy and severe disease efficacy rates respectively. These numbers are from clinical trials, some of which are continuing to enroll and follow-up patients. These numbers may change, and a 100 percent efficacy is not expected to carry over in real-world settings but are indicative of high efficacy.
| Vaccine | Clinical Disease Viral Efficacy | Severe Disease Viral Efficacy |
| Pfizer | 95% | 89% |
| Moderna | 94% | 100% |
| Astra | 62% | 100% |
| Sinovac (Brazil trial) | 50% mild 78% moderate | 100% |
In the past two weeks, encouraging data from phase 3 studies of several more vaccines have been released. If confirmed, this means more safe and efficacious vaccines are on the way. These vaccines are J&J/Janssen, Gamaleya, and Novovax and their tentative efficacies are listed in the table below.
| Vaccine | Clinical Disease Viral Efficacy | Severe Disease Viral Efficacy |
| J&J/Janssen | 66% moderate to severe | 85% |
| Gamaleya | 94% (interim) | 100% |
| Novovax | 89% (interim) | Not reported |
There are other vaccines that have reported phase 3 data but are difficult to verify from primary sources. There will be better clarity when more data is released.
Vaccines are administered through a variety of platforms with different active components for inducing immunity. With the current data, four vaccine platforms now have at least some phase 3 data showing good efficacy and safety. These four vaccine platforms with good data are nucleic acid-based, recombinant viral vectored, whole inactivated virus, and spike protein. The mRNA vaccines from Pfizer and Moderna are examples of nucleic acid-based vaccines. Recombinant viral-vectored vaccines are those produced by Astra, Gamaleya, and J&J. Sinovac is a whole inactivated virus vaccine. Novovax uses the spike protein platform. On the way are many more vaccines using these different platforms, and there is reason to be optimistic. Two other platforms using virus-like particles and live attenuated virus are still in development. These platforms may turn out to have better transmission-blocking properties. Last week’s column went over all six platforms in detail and why each of them may have a role to play in defeating Covid-19.
Having many platforms for vaccines is a good way of ensuring that vaccines remain effective even in the face of variants. This is like having a whole range of antibiotics for bacteria as opposed to using only amoxicillin all the time. There is a lesser chance of developing resistance and loss of vaccine efficacy. There is already some evidence some of the current vaccines are less effective against the South African variant. Vaccines that start losing efficacy can be tweaked by modifying or adding components to cover the variants that are circulating, much like the influenza vaccine.
Early vaccine rollouts showing exciting results
Israel has been one of the fastest countries to roll out vaccines for its adult citizens, with about 40 percent of their population having received at least one dose. In just three short weeks from the first dose, there are already significant drops in hospitalizations and infections among those vaccinated. Israel is using the Pfizer vaccine, which has shown excellent clinical efficacy with its two-dose regimen. The fact that hospitalizations are already dropping with just one dose underlines the positive effects of rolling out the vaccination program as soon as possible. The Israel experience will inform the global vaccine program and guide countries on best practices.
Follow-up studies for the currently approved vaccines are starting to show value-added features. The UK rollout of the Astra vaccine, with a second dose given up to 12 weeks from the first dose is showing a better-than-clinical trial efficacy of 82 percent. It is very rare for real-world performance to outdo controlled clinical trials, so the increased efficacy may suggest that a longer interval between the first and second dose for some vaccines may improve performance. This was also seen in the Sinovac Brazil trial where the prescribed 14-day interval for the second shot was delayed for some patients by at least one week. Those subjects with a delayed second dose showed a 20 percent higher efficacy rate than those who got it on time. More studies are needed to confirm this, but real-world experiences can further fine-tune and optimize the use of the current Covid-19 vaccines.
Sterilizing immunity
Additional data from the Astra vaccine trials seem to show it may induce some sterilizing immunity that can interrupt transmission in up to two thirds of patients after the first dose. Sterilizing immunity is the phenomenon of a vaccine completely interrupting transmission by preventing a virus from ever gaining a foothold in the body. This occurs when a vaccine produces high levels of neutralizing antibodies, which effectively kill the virus upon entry.
This new data is similar to previous preliminary findings from the Moderna and Pfizer trials that show both Covid-19 vaccines can interrupt even asymptomatic infection to a certain level. This is still early data and should be interpreted with caution because sterilizing immunity can wane over time. A drop in antibody levels can result in lower protection from infection and may still allow an asymptomatic or mild infection to be established, which can then be passed on. Fully vaccinated individuals who have received the current crop of vaccines still need to adhere to minimum health standards and protocols since they may still harbor and transmit infection even if they are protected from developing symptoms. The quest for transmission-blocking vaccines continues, but the ones available now are very good at preventing clinical and severe disease.
So far, there is no one vaccine that has been shown to induce complete sterilizing immunity. Such a vaccine is ideal because it can completely interrupt transmission and lead to herd immunity. Some of the vaccines may eventually be proven to do this, but it is a loftier goal for which proper studies need to be done. This is not a dealbreaker, however. There is every reason to be optimistic that current vaccines will deal the virus a severe blow, and more weapons are in the works.
Even without sterilizing immunity, getting the vaccines out to as many people as soon as possible will save lives and decrease infections. At a practical level, asymptomatic people are 10 to 20 times less likely to transmit disease than symptomatic ones since asymptomatic people don't cough or sneeze. Aside from expecting a steep drop in deaths shortly after the current crop of vaccines are deployed, there will also likely be a significant drop in transmission. At that point, the economy may be further reopened, and life may slowly return to what it was before Covid-19. For a world that has grown pandemic-weary, that is the best news of all.