SciMoms COVID FAQs: Will a COVID vaccine be safe and effective?

In this series of COVID FAQs, the SciMoms answer your frequently asked questions about the novel coronavirus or COVID-19 pandemic. In this section, Alison and Layla focus on COVID vaccines and whether a COVID vaccine will be safe.

What is a realistic vaccine timeline?

Since the summer, most vaccine experts have proposed the following ambitious vaccine timeline

  • Fall 2020: data is collected to determine if a COVID vaccine will be safe and effective
  • Early 2021: FDA approval of some combination of the vaccines currently in Phase III trials 
  • Early-Mid 2021: Initial vaccinations available to specific groups like healthcare providers, vulnerable groups, and essential workers/responders
  • Mid-late 2021: Distribution expands 
  • Late 2021-2022 and beyond: General and widespread vaccination programs

While this COVID-19 vaccine timeline is exceptionally ambitious, faster than the development timeline for any other vaccine, the development so far is managing to keep pace. This accelerated timeline is due to the extraordinary resources that have been dedicated to development, and the single-minded focus and unprecedented collaboration of researchers worldwide in both the public and private sectors. 

These best-case scenarios estimated that we would have results of Phase III trials in November. In fact, Pfizer and Moderna announced the first round of preliminary results showing greater than 90% efficacy from Phase III trials in early November. 

An important caveat is that so far all that these companies have shared are press releases. No vaccines have been approved, and their results have not been reviewed or vetted by any governmental agency or other scientists. 

Both companies announced that they plan to apply for emergency use authorization (EUA) in the 3rd week of November. On November 20, Pfizer submitted an application for EUA for its vaccine. Once an EUA application is submitted, the FDA would begin review of the data. Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, has stated that any review will “take the amount of time that we need to take” to ensure that the data is of sufficient quality to support an approval. Providing a transparent approval process is essential for the public to trust the safety and efficacy of the COVID vaccine.

Based on current progress, this timeline appears to be realistic, and we are on track to have at least one vaccine available within the projected time frame. 

Resources

When Will You Be Able to Get a Coronavirus Vaccine?

Covid-19 Vaccine Tracker: Latest Updates

When will we have a vaccine for COVID? When will life return back to normal?!

FDA’s Peter Marks on the coronavirus vaccine review process

What are companies and government agencies doing to meet this timeline?

Companies, government agencies, non-governmental organizations, and nonprofits have all taken specific actions to meet the COVID vaccine timeline and proactively address potential problems of development, testing, production, distribution, and trust.

Development and testing: Funding was provided to many companies and researchers very early in development, including groups using new RNA based vaccine technology. This funding allowed scientists to start developing vaccines with only the genetic sequence, which was shared publicly online in January, before the disease or the virus even had an official name.

COVID vaccine challenge trials are being conducted to expedite the collection of efficacy data and to ensure the vaccines are safe. These studies are more controversial because they involve deliberately exposing healthy volunteers to SARS-CoV2. These trials can be completed faster because you don’t have to wait for people to get sick. However, many are concerned about the ethics of such trials. Some argue that the risk is worth the lives saved by shortening the time to an effective vaccine. Others argue that given all the other ways we can accelerate development, these trials are unethical. 

Production and distribution: COVID vaccine manufacturers have expanded their production capabilities while they are developing and testing the vaccines to ensure they are safe. Typically, companies would not invest extensive resources into production and distribution before having some evidence that the vaccine will be approved. However, in this case, specific steps of the process (especially relating to production and distribution) have occurred simultaneously rather than sequentially. Investments and grants from many sources were provided to support this, greatly accelerating the vaccine distribution timeline. In the United States, Operation Warp Speed has allocated military personnel to distribute vaccines across the country as quickly as possible.

One of the distribution problems, particularly with the mRNA vaccines, is that they require storage at very cold temperatures (negative 80 degrees celsius). This storage requirement means that these vaccines cannot be given at most pharmacies and doctors’ offices. However, they may be available instead at large medical centers or vaccine centers with the infrastructure to store these vaccines properly. Vaccines that require special storage will be more difficult to distribute in rural areas or countries lacking the infrastructure found in concentrated urban centers in more developed countries. 

Some of the vaccines currently in Phase III trials require two shots, compounding production and distribution problems. The need for multiple doses also adds a logistical problem of how to get people to return for a second dose. 

To address these and other issues related to distribution, the National Academies of Sciences, Engineering and Medicine have developed “A Framework for Equitable Allocation of Vaccine for the Novel Coronavirus” to help policymakers in the US and around the world ensure equitable distribution of COVD vaccines. The WHO has also issued guidance to ensure the fair allocation of vaccines worldwide.

Trust: It’s not only timing that is important for rolling out a COVID vaccination program. The success of these vaccines ultimately depends on enough people getting the vaccine (See FAQ: How do we achieve herd immunity?). If people do not trust that the COVID vaccine is safe and effective, a significant percentage of people may not be willing to get the vaccine. Anti-vaccine activists have been ramping up their rhetoric for months and allying with alt-right, anti-mask, anti-lockdown groups. This rhetoric plus the growing partisanization of science, may mean that  even people who support vaccines may not trust this particular vaccine

Government agencies and companies must be transparent with data and the approval process. They must discuss these issues openly and address them proactively to ensure the successful distribution of COVID-19 vaccines.

Resources

How the world made so much progress on a Covid-19 vaccine so fast

Coronavirus (COVID-19) Update: FDA Takes Action to Help Facilitate Timely Development of Safe, Effective COVID-19 Vaccines

Framework for Equitable Allocation of COVID-19 Vaccine

Fair allocation mechanism for COVID-19 vaccines through the COVAX Facility

Digging the Rabbit Hole, COVID-19 Edition: Anti-Vaccine Themes and the Discourse Around COVID-19

COVID-19 Science Has Become Partisan. Who Can You Trust?

Is the vaccine being rushed?

While this timeline is ambitious and faster than any other vaccine in our history, the process is not being rushed. “Rushed” implies that COVID vaccine manufacturers are taking shortcuts or that government agencies are not thoroughly testing vaccine candidates to ensure they are safe. There is no evidence of this, despite political rhetoric about rushing a vaccine to approval without complete testing. Vaccine manufacturers and the government agencies responsible for vetting vaccines have committed to not cutting corners on testing and approval.

One reason why the development process has been expedited is that vaccine developers did not start from scratch. Previous research on the coronaviruses SARS and MERS allowed vaccine researchers to get a jump start on SARS-CoV2.

The unprecedented levels of resources and scientific collaboration devoted to COVID research, combined with labs pivoting to work on SARS-CoV2, have also helped the research move quickly. In January and February of this year, researchers around the world were already coordinating and collaborating in their research .  

Most importantly, even though the research and development has been accelerated, the vaccines will still need to go through all the required testing and vetting to ensure that the COVID vaccine is safe and effective before approval. It will also need to undergo post-approval monitoring (See “How will we know a vaccine is safe?”).

Resources

Ensuring the Safety of Vaccines in the United States

Questions and Answers About COVID-19 Vaccine Clinical Trials | University of Michigan

FDA COVID vaccine chief: We’ll be independent, transparent, trustworthy

How will we know a COVID vaccine is safe?

Despite the recent political rhetoric about accelerated approval of a SARS-CoV2 vaccine before trials are completed, our institutions and guidelines around vaccine approval remain strong. Pharmaceutical companies and government agencies continue to push back against this rhetoric and support the appropriate level of scrutiny for vaccines. 

“We are committed to expediting the development of COVID-19 vaccines, but not at the expense of sound science and decision making. We will not jeopardize the public’s trust in our science-based, independent review of these or any vaccines. There’s too much at stake.”- Stephen M. Hahn, M.D., FDA Commissioner, and Peter Marks, M.D., Ph.D., Director, Center for Biologics Evaluation and Research

In short, the FDA, CDC, and the Advisory Committee on Immunization Practices (the agencies that participate in vaccine approval and recommendations) will apply the same standards these agencies apply to all vaccines to COVID vaccines.

How a new vaccine is developed, approved and manufactured: describes clinical trials phases and criteria for vaccine approval
How a new vaccine is developed, approved and manufactures (CDC)

As we wrote above, trust is essential. Government agencies and companies must be transparent with their data and the approval process to ensure the successful and safe distribution of COVID-19 vaccines.

In the Resources section below, we have shared articles that explain these standards and procedures in detail. 

Resources

Calm down about political ‘mischief’ around COVID-19 vaccines, scientists say

Ask SciMoms: Where does the vaccine schedule come from?

How Scientists Determine If A COVID-19 Vaccine Works

Vaccine Testing and Approval Process

The Drug Development Process

Will vaccines continue to be monitored after a vaccine is approved?

Yes, as with all vaccines in the US, COVID vaccines will be monitored through existing surveillance programs after vaccination to ensure they are safe. Post-approval monitoring and study is a normal part of the vaccine approval and monitoring system in the US.

Programs that monitor vaccine safety include the Vaccine Adverse Event Reporting System (VAERS), the Vaccine Safety Datalink, the Post-Licensure Rapid Immunization Safety Monitoring, and the Clinical Immunization Safety Assessment Project. All of these monitoring programs watch for adverse events and possible side effects. These programs ensure that potential risks associated with vaccines are identified and reviewed by ACIP.

Ongoing clinical trials are also essential to determine the vaccine’s efficacy over time, as well as the need for boosters. These studies are reviewed three times a year by ACIP, as we explained in our previous post on the vaccine schedule. If ongoing studies identify that immunity is declining over time, then the vaccine schedule may be modified to include a booster shot. 

How a vaccine's safety continues to be monitored: explains how vaccines are monitored for safety after the public begins using the vaccine
How a vaccine’s safety continues to be monitored (CDC)

To continue ensuring that COVID vaccines are safe, they will be subject to the same monitoring before and after approval as all other vaccines in the US.

Resources

Vaccine Safety Monitoring | Vaccine Safety

Is the vaccine being tested on children? 

A COVID vaccine candidate will not be tested in young children until it is found to be safe and effective in adults. This is standard practice for vaccine trials and reflects the FDA’s guidance on COVID vaccine trials. As a result, the COVID vaccines will likely be available for kids after it is available for adults.

Pfizer recently received approval to test its vaccine in adolescents, but, as of this writing, no other trials are including children. Many doctors and researchers are calling for the development and testing of children’s COVID vaccines to start now. The American Academy of Medical Colleges article provided below in Resources describes the issues surrounding pediatric vaccines for COVID in detail.

Once these vaccines are tested in children, they will undergo all of the same processes for approval and post-approval monitoring described in the sections above.

Resources

We can’t defeat COVID-19 without vaccinating children. There aren’t even any kids’ clinical trials yet

Is it true that kids are not being included in the current COVID-19 vaccine Phase 3 trials?

What does it mean if a vaccine trial is paused? 

Some of the COVID vaccine trials were recently paused (and then restarted) because an adverse event occurred. An adverse event is any unexpected medical incident that occurs during a clinical trial, whether it is related to the vaccine or not. A pause allows researchers to investigate whether the event was related to the vaccine and whether continuing the trial puts participants at unacceptable levels of risk.

Such pauses are not unusual in clinical or vaccine trials and are part of standard safety reviews. When a trial is paused, it means that researchers are appropriately monitoring and investigating the safety of these therapies. Ultimately, it is not surprising that several COVID vaccine trials have been paused due to adverse events. Clinical trials can be paused or stopped for three reasons.

  1. Overwhelming effectiveness: If the benefit is so clear and apparent, the clinical trial is stopped so the placebo participants can get the drug.
  2. An adverse event, serious side effect, hospitalization, or death.
  3. Futility: If it becomes clear that the drug doesn’t work as well or better than existing drugs, the trial is typically halted to allow participants to stop taking an inferior treatment.

All of these COVID vaccine trials were eventually restarted because there was no indication that the vaccine caused the events or that they were not safe. Adverse events will be included in the documentation of the trial. In fact, all adverse events that occur during a clinical trial are always listed in the product insert, even if causation cannot be determined. 

Resources

Understanding Side Effects and Adverse Events | Vaccine Safety

The Global Vaccine Safety Initiative (GVSI)

Covid-19 vaccine trials from AstraZeneca, Johnson & Johnson to restart

Will mutations of the SARS-CoV2 virus make vaccines ineffective?

So far, the data show that the genome of SARS-CoV2 is mutating quite slowly, at half the rate of influenza and a quarter of the rate of HIV. There is also no evidence that the mutations in SARS-CoV2 change the ability to spread or cause disease. Importantly for vaccine development, none of the known mutations appear to modify viral proteins in ways that prevent antibodies from recognizing the virus. Fortunately, this suggests that we will develop a vaccine without regularly needing a new version as we do for the flu. Given what we know about declining immunity to coronaviruses in general, we may need regular boosters.

Resources:

What happens if COVID-19 mutates?

COVID-19 Will Mutate — What That Means for a Vaccine

Is the SARS-CoV-2, the virus that causes COVID-19, mutating and if so, does it matter?

The coronavirus is mutating — does it matter?

Does a vaccine need to be “perfect” to help?

No. No vaccine is “perfect” (100% effective), yet we have controlled many diseases with these “imperfect” vaccines. The FDA has stated that the COVID-19 vaccine should be at least 50% more effective than a placebo to receive approval. This means that for every 100 people vaccinated and 100 people getting a placebo, half as many people in the vaccine group will get the disease compared to those in the placebo group. 

These numbers highlight one reason why the clinical trials take time. To calculate efficacy, people enrolled in coronavirus trials have to continue living their lives as “normal,” following the CDC’s guidelines as best they can. Only once a certain number of people in the trial have tested positive for COVID-19 can scientists compare the number of people in each group who were infected. At that point, researchers calculate the efficacy of the vaccine and identify any undesired trends or complications. In an ironic yet heartbreaking way, the uncontrolled spread of COVID-19 in the United States has accelerated these trials, since people encounter the virus much more quickly than they would if our community spread were not out of control.

Fifty percent may not sound very impressive, but reducing the number of people susceptible to infection would significantly affect the spread of disease, even if it’s not perfect. In addition, many vaccines, like the flu vaccine, reduce the severity of disease and the rate of hospitalizations. A vaccine that keeps people out of the ICU and increases survival would also be hugely beneficial.

In encouraging news, early data from Phase III trials suggest that some vaccine candidates are far exceeding these benchmarks, with preliminary efficacy data of over 90%. As discussed above, this data has only been shared via press release. These results have not been reviewed or vetted by any governmental agency or other scientists. 

Resources

Why A COVID-19 Vaccine That’s Only 50% Effective Could Still Help Stop The Pandemic: Shots – Health News

What happens if not enough people get vaccinated?

If we have an effective vaccine that is approved, but not enough people get it, the pandemic will continue. Vaccines can only help end the pandemic if enough people get them. As we discussed above, ensuring that people get the vaccine requires trust, equitable distribution procedures, and serious logistical coordination will become critical. 

Whatever the efficacy of an approved vaccine, until we reach the herd immunity threshold, we need to continue preventative measures, such as masks, physical distancing, regular testing, frequent handwashing, and contact tracing in order to contain the spread of the virus within communities. We will need a combination of these measures to end this pandemic. This is a good place for a reminder that we have only ever eradicated one disease, and maintaining elimination takes active steps to prevent outbreaks. See our Immunity FAQ for details.

As we discussed in our FAQs on immunity, we can reach herd immunity naturally or through vaccination programs. Widespread vaccination will significantly accelerate how fast we can achieve this threshold without the mortality and morbidity associated with natural immunity. But vaccines on their own will not end this pandemic.

Will a vaccine eradicate COVID-19?

It seems unlikely. We have only ever successfully eradicated one disease in humans: smallpox. If the vaccine has lower efficacy, the percent of the population that will need to be vaccinated will be very high. Even a very effective vaccine will only be useful if people actually get it, as discussed in the previous questions. Issues of access and trust may lead people to decline the vaccine, or be unable to get it (see above). 

We may be able to eliminate SARS-CoV2 from certain areas (as some countries have been able to do without a vaccine). However, vaccination programs and preventative measures will still be needed to prevent future outbreaks (see our previous FAQ for an explanation of elimination and eradication).

Do we need a vaccine before anything can return to normal?

No. Many countries around the world have returned to a much more normal existence without a vaccine. Sadly, the situation the US currently finds itself in was not necessary. Had we stayed home and followed public health officials’ instructions when the pandemic first broke out, we could have contained the virus. If we had truly controlled the spread in the spring and early summer, we could have reopened and not had the continued surges of this pandemic that we see today. Some countries were able to contain the virus effectively, and safely reopen. 
We are currently in a stage of uncontrolled spread, limited contact tracing, and no widespread, frequent, or fast testing. Consequently, there’s no real way to safely return to “normal” without a vaccine. However, as discussed above, even with a “perfect” vaccine, we still need to take precautions to fully control this disease. We should not rely on the magic bullet of a vaccine or wait until we have a vaccine to take these precautions.

Who will get the COVID-19 vaccine first?

The CDC developed guidelines for who will get a COVID-19 vaccine first if there are not enough doses to vaccinate everyone when it is first approved. Similar decisions for vaccine prioritization are being made in Canada. The draft guidelines are aimed at minimizing death and stopping disease spread as much as possible by prioritizing these populations:

  • Healthcare personnel
  • Workers in essential and critical industries
  • People at high risk for severe COVID-19 illness due to underlying medical conditions
  • People 65 years and older

The US National Academies of Sciences, Engineering and Medicine proposed a tiered five-phase plan to allocate a coronavirus vaccine to US residents fairly. This proposal and the WHO plan are more detailed and consider issues like occupation and health disparities.

Resources

Framework for Equitable Allocation of COVID-19 Vaccine

Fair allocation mechanism for COVID-19 vaccines through the COVAX Facility

US advisory group lays out proposal on how to prioritize Covid-19 vaccine

Who gets a COVID vaccine first? Access plans are taking shape

What kinds of vaccines are being tested?

A few facts to remember here:

  • Viruses are infectious agents that can only replicate inside a living host cell. They consist of genetic material (RNA or DNA) wrapped in protein and sometimes lipid membranes.
  • Antibodies are proteins that are produced by the immune system when specialized cells detect the presence of something that they do not recognize as part of your body. Antibodies are the critical mediators of the adaptive immune response.
  • Vaccines work by teaching your immune system to make antibodies that recognize a disease-causing agent without getting sick.
  • When you get infected with something you are vaccinated against, the immune system “remembers” how to make the antibodies so it can trigger an immune response to fight the infectious agent, preventing illness.

For more details, see our previous FAQs.

Protein-based vaccines: These vaccines contain viral proteins but no genetic material. These can be whole proteins or pieces of proteins. The immune system then makes antibodies that recognize these proteins. An example is the pertussis vaccine. 

Viral vector vaccines: These vaccines contain viruses that are engineered to carry genes from SARS-CoV2. These viruses infect our cells, and the cells make this protein. Our immune systems then make antibodies that recongize this protein. There are no existing viral vector vaccines for humans (only veterinary vaccines currently use this technology).

Genetic vaccines: These vaccines contain mRNA or DNA that encode a viral protein. Our cells then make this protein, and our immune system makes antibodies that recognize the protein. There are no existing genetic vaccines available.

Both the Moderna and Pfizer vaccines that have released preliminary data as of this writing are mRNA vaccines. These vaccines have moved so quickly from basic science to clinical trial because researchers can very quickly produce the mRNA once they know the viral sequence. From the publication of the genetic sequence of SARS-CoV2 on January 10, 2020 to the first Phase I clinical trial was only 66 days. These are the first vaccines to be tested using this new technology.

Inactivated or Attenuated Viruses: These vaccines contain viruses that have been weakened or killed by chemicals. They cannot cause disease but are still able to trigger the production of antibodies. Examples include the MMR vaccine and the yellow fever vaccine.

Repurposed Vaccines: These are vaccines for other diseases that might protect against SARS-CoV2. 

Resources

Covid-19 Vaccine Tracker: Latest Updates

Drug Targets / Technologies: Vaccine Technology

RNA vaccines: an introduction

What Makes an RNA Vaccine Different From a Conventional Vaccine?

Which COVID-19 vaccine will be best?

As discussed above, the regulatory process ensures that any approved COVID vaccine is safe and effective. If we end up in the fortunate position of having several COVID-19 vaccines approved, then we can have confidence that all of these options are safe and effective. Other diseases have multiple vaccine options, so this would not be an unusual outcome. It typically doesn’t matter which one you get, as any approved vaccine has gone through the rigorous process in order to gain approval.

However, sometimes vaccines are approved for specific age groups or particular circumstances. Determining these restrictions is part of the approval process. For COVID-19 vaccines, we have already discussed above that approval in children will likely occur after approval for adults. As a result, we may end up with different vaccines approved for different age groups. Vaccines can only be offered to people in groups for whom it is approved.

Resources

Vaccine Testing and Approval Process

When will SciMoms decide to vaccinate their children with new COVID-19 vaccines?

The SciMoms have discussed this topic at length. We will vaccinate when the COVID-19 has been rigorously tested according to current vaccine standards. We will feel confident when vaccines are approved by the FDA’s current standards for clinical trials, vetted by ACIP, and reviewed by medical organizations such as the American Academy of Pediatrics and the American Medical Association. We are confident that the current process is working, which is why we support upholding the current regulatory framework. 

SciMoms COVID FAQs