The news traveled thick and fast. The Pfizer vaccine against Covid-19 works! Scientists were optimistic for months that a Covid-19 vaccine would be developed, but nothing was guaranteed. Proof that it would be efficacious was building up, with phase 1 and phase 2 trials giving way to phase 3 trials without much fanfare. In the context of vaccine development, this was a very good sign, as any major safety issues usually come out during these early phases.
WAITING WITH BATED BREATH
Many infectious disease doctors and vaccinologists were waiting with bated breath. There had been tantalizing data about robust antibody responses among many of the vaccine candidates. The only thing left to prove was that it worked in a clinical setting. It did.
Very few things, however, are clear at this point. The initial press release had sparse details on efficacy, although more information was available afterward. The biggest question was whether it worked. The answer was a resounding yes, at least in terms of outcomes they defined. Out of the 94 cases of symptomatic Covid-19 that developed during the trial, 90 percent occurred in the placebo group. This means that the vaccine prevented clinically apparent Covid-19 disease among those who were inoculated.
The 90 percent efficacy is much better than expected, beating 50 to 70 percent efficacy predictions for first generation vaccines. The trial has not been completed, but this interim analysis showed that the vaccine is doing what it is supposed to do.
The next big question is how it works. Is it a transmission-blocking vaccine, or a disease-modifying vaccine? Transmission-blocking vaccines induce antibody responses strong enough to neutralize virus particles. The virus does not spread from the vaccinated individual. This is similar to what the oral polio vaccine (OPV) does. OPV gives the body enough immunity to completely destroy any polio virus that enters the body. In contrast, disease-modifying vaccines induce just enough of an immune response to block the development of severe disease, but do not necessarily kill all the virus particles.
Disease modifying vaccines do not completely prevent multiplication and transmission of viruses to the next susceptible individual, although they may still have some effect on infectivity. The inactivated polio vaccine (IPV) is a disease-modifying vaccine. IPV prevents deadly polio complications such as encephalitis and paralysis, but some level of viral replication still occurs. This means that while people are protected from clinical disease, the virus continues to circulate in the community.
TRANSMISSION-BLOCKING VERSUS DISEASE-MODIFYING
Why not develop transmission-blocking vaccines exclusively? Why bother with disease-modifying vaccines? Despite the many advantages to transmission-blocking vaccines, these carry greater risk. They are also trickier to develop. Transmission-blocking vaccines typically use the whole virus and most are live though weakened. There is a small chance of the weakened virus reverting to a more virulent form. This occurred with the OPV, the main reason why many programs shifted from OPV to IPV. Since OPV was so successful at blocking transmission, the number of polio cases dropped dramatically. When naturally occurring polio cases became very rare, the weakened virus from OPV was more likely to cause a few cases of polio than any wild polioviruses left in the environment.
Newer vaccine development techniques can increase the chances of a transmission-blocking effect using genetically modified virus, while minimizing the risk of clinical disease from the vaccine.
Due to the urgent need to prevent further deaths, however, any vaccine against Covid-19 is welcome whether it is transmission-blocking or disease-modifying.
There isn’t enough data in the press release to determine whether the Pfizer vaccine could be a transmission-blocking vaccine. The trial was designed to look at how many people developed symptoms of Covid-19—typically fever, cough, and colds.
VIRUS COUNTS AND CULTURE
If they got sick, they were tested for Covid-19 with an RT-PCR assay. Since approximately 30 percent of Covid-19 are either asymptomatic or have very few symptoms, this trial design will miss those patients. We need to know if virus counts and cultures were done, to see whether vaccinated individuals shed less or no virus compared with participants who received placebo. Whether or not the Pfizer vaccine only resulted in milder disease or it was able to decrease viral counts and thus transmission, it’s still going to be a useful vaccine. A vaccine that decreases the risk of symptomatic disease will likely decrease the risk of severe to critical disease. The risk of developing severe to critical disease was later added as another outcome to be measured. It will take some time to completely understand just how good this vaccine is but finding a vaccine that works represents a major step in the right direction.
Other issues that need to be addressed include the longevity of the immune response, the long-term safety data, and the logistics for rolling out the vaccine. It is unclear whether Covid-19 infection and recovery confer temporary or lifelong immunity. This uncertainty extends to the vaccine. There have been reports of reinfection in recovered patients, although these are likely uncommon. The bulk of the data suggests that recovery from infection confers at least a few months of immunity, and we can extrapolate that to the vaccines. A vaccine that will work for even just a year will still be useful, and boosters can be given if indicated.
The Pfizer vaccine is a two-dose regimen given three weeks apart. Two-month safety data will be available by the third week of November. If all goes well, this safety data will be good enough for the US FDA to authorize emergency use. Pharmaceutical companies continue to collect longer term data even after clinical trials are over. Surveillance after the vaccine has been released for use by the general population can detect rare side effects.
Dr. Anthony Fauci of the United States National Institutes of Health stated that he expects the Pfizer vaccine to be available for limited use by January 2020, and for general use by April 2020.
A major hurdle for use of this vaccine in the Philippines is the need for storage at -80°C. Very few places in the Philippines have this refrigeration capability. There are other vaccines in development that can be stored at 2 to 8°C, but we do not know if they will be as efficacious, or if they will be effective at all. It is a good thing there are more than 100 vaccines in development, since some are single-dose and some require less stringent refrigeration. The chance of those vaccines working has been boosted by the demonstration that at least one vaccine works, although safety and longevity issues still need to be worked out.
Finally, there is the issue of acceptance of the vaccine by the public. There is antivaccine sentiment, and surveys in the US report as much as one third of people will decline the vaccine over perceived safety issues. In the Philippines, the recent Dengvaxia fiasco is still fresh in many people’s minds. With hope, everyone has learned their lessons on safety. Meticulous protocols need to be in place to detect any problems, and the public needs to be assured that even though the process was accelerated, the proper safeguards were still followed.
This pandemic has truly altered our day-to-day existence. The discovery of an effective vaccine will enable us to return to a semblance of normalcy. People have forgotten how life-changing vaccines can be. Smallpox has been eradicated.
Lifetime encasement in iron lungs for those children paralyzed by polio are a thing of the past. Birth defects from maternal German measles are almost unheard of. These are just some of the ways our society has been changed by the discovery of vaccines. Perhaps after all this, we will never take vaccines for granted ever again. An effective Covid-19 vaccine is just the latest in a long line of discoveries that show how science has transformed our lives for the better.