COVID-19 Vaccine FAQs

March 17, 2021

This article was originally published Dec. 4, 2020 and has been updated by the author.

Since the beginning of the pandemic, little has generated more anticipation (or hesitancy) than the promise of a COVID-19 vaccine. Less than a year after the World Health Organization declared COVID-19 a pandemic (March 11, 2020), that “promise” became a reality, when 2 major pharmaceutical and biotech companies, Pfizer (in partnership with BioNTech) and Moderna, Inc., announced unprecedented success following the primary efficacy analyses of their Phase 3 COVID-19 vaccine trials. By mid-December 2020, both Pfizer and Moderna were issued Emergency Use Authorization (EUA) by the U.S. Food & Drug Administration (FDA). Not long after, Johnson & Johnson (J&J) also reported promising results from its Phase 3 vaccine trials and became the first single dose COVID-19 vaccine to receive EUA in late February 2021. Today, all 3 vaccines have been authorized in several countries and are being actively distributed. Outside of the U.S., additional COVID-19 vaccines, including Sputnik V, Sinovac, Gamaleya, Bharat-Biotech and Oxford-AstraZeneca have also been authorized for emergency use. Concurrently, there are 75 vaccines being tested in clinical trials, 21 of which have reached the final stages of testing (as of March 11, 2021). 
Data from these studies are amongst the most pivotal advancements in the fight against COVID-19, to date. But amidst all the buzz, questions and misinformation continue to circulate, making it more vital than ever that the general public, and scientists alike, have a thorough understanding of what goes into and is coming out of these trials. One thing is certain: the success or failure of any vaccine depends as much on public acceptance as it does executive authorization.

How do Pfizer, Moderna and J&J vaccine platforms compare?  

At the outset, the Pfizer and Moderna vaccines appear to be similar in structure and function. Both vaccines use mRNA platforms, a gene-based technology that has long been explored for its disease prevention and treatment potential but has generated little quantifiable success in the vaccine department, due primarily to engineering challenges...until now. Within a week’s time (Nov. 9-16, 2020), both companies reported their vaccine candidates to be more than 90% effective at preventing symptomatic COVID-19, and many are hoping these advancements in mRNA technology will revolutionize vaccine science.  
The J&J vaccine differs from Pfizer and Moderna in that it uses a viral vector platform, which relies on a harmless, recombinant adenovirus, to help deliver its targeted genetic message to host cells. This type of vaccine is not entirely new to the company, as J&J uses the same viral vector platform in the initial dose of their Ebola vaccine, which became the first FDA-approved vaccine for the treatment of Ebola virus disease in December 2019. At the end of January 2021, J&J reported its COVID-19 vaccine to be 72% effective at preventing moderate to severe disease in the U.S. and 66% effective amongst all trial participants. 

How do mRNA vaccines work? 

mRNA vaccines are synthetic in design. The Pfizer and Moderna vaccines both consist of messenger RNA (mRNA) encoding a prefusion stabilized form of SARS-CoV-2 spike (S) protein, surrounded by a lipid nanoparticle coat, which protects the mRNA from enzymatic degradation before it reaches the protein-making machinery (ribosomes) of host cells. 
S protein is the portion of SARS-CoV-2 that binds to human ACE2 receptors. It is characteristic of SARS-CoV-2, required for infection and has been identified as a viable antibody target. Vaccination delivers a genetic message that signals host cells to produce copies of this antigen. Ribosomes translate the mRNA and initiate host production of spike protein copies. Then antigen-presenting cells display the antigen on their surfaces, triggering the immune system to produce antibodies and T-cells in response to the foreign protein.
COVID-19 mRNA Vaccine Infographic
Depiction of mRNA vaccine-induced antibody response against SARS-CoV-2 spike proteins.
Source: American Society for Microbiology

How do viral-vectored vaccines work?

Viral-vectored vaccines are based on another type of next-generation platform that’s more stable and less expensive to manufacture than mRNA vaccines. These vaccines use modified forms of viruses, other than the target pathogen, to carry genetic messages to host cells. The J&J vaccine uses a recombinant adenovirus called human adenovirus type 26 (Ad26). It is a double-stranded DNA virus that has been genetically modified to be replication deficient and therefore incapable of causing infection. 

Like Moderna and Pfizer, J&J targets the SARS-CoV-2 spike protein. DNA encoding the S gene is added to Ad26. Vaccination introduces the resultant, specialized viral vectors to host cells. Once engulfed, the adenovirus pushes its DNA into the nucleus of the host cell, but because its own DNA has been modified to be non-replicating, the gene encoding S protein is the only thing that gets copied and transcribed into mRNA. That mRNA then leaves the nucleus to be subsequently translated by ribosomes and initiate host cell production of S protein. Antigen-presenting cells then display the antigen on their surfaces, and the immune system begins producing antibodies and T-cells against the foreign protein. 

Is it possible for someone to contract COVID-19 from these vaccines? 

No. Because these vaccines use the genetic code of a single virus protein to generate an immune response, they cannot cause SARS-CoV-2 infection in vaccine recipients. Furthermore, the adenovirus used for the J&J vaccine is genetically engineered to be unable to replicate or cause infection inside of host cells.

How were the studies conducted and what do the data show? 

When a vaccine trial hits Phase 3, the product is being actively tested in large populations of humans. Both Pfizer’s and Moderna’s Phase 3 trials were randomized, observer blinded, 1:1 placebo-controlled studies. Enrolled participants were randomly administered a predetermined dosage of vaccine (30 µg for Pfizer and 100 µg for Moderna) or a placebo saline injection, and those in charge of measuring, recording and assessing the trial did not know who was assigned to each group. 
The mRNA vaccines both rely on a 2-dose regimen that must be administered 3-4 weeks apart. Pfizer injections were given 21 days apart, while Moderna injections were given 28 days apart. The primary endpoint of these studies was laboratory confirmed, symptomatic COVID-19, and researchers began evaluating cases 7 days post-injection with the second dose of Pfizer’s vaccine (or placebo) and 14 days post-injection with the second dose of Moderna’s vaccine (or placebo). At that point, if a patient developed symptoms of disease and tested positive for COVID-19, trial records were consulted in order to determine if that participant had been given the vaccine or placebo. 
J&J’s Phase 3 vaccine trial was also randomized, double blinded and placebo controlled. Enrolled participants were randomly administered a single dose of vaccine, at a dose level of 5x10^10 virus particles, or given a placebo injection. Efficacy was evaluated 14 and 28 days post-injection. 

Data from the Moderna and Pfizer Phase 3 trials have been published. However, at this time, the Phase 3 analysis of the J&J vaccine has only been publicized as press releases, and the publication of complete study data is still pending. 

  • 43,538 enrolled participants.
  • 150 clinical trial sites in 6 countries and 39 U.S. states.
  • 42% of global and 30% of U.S. participants came from racially and ethnically diverse backgrounds. Pfizer provided a further breakdown of these demographics.
  • 41% of global and 45% of U.S. participants aged 56-85. 
  • 95% efficacy was reported after the final analysis of Pfizer’s Phase 3 COVID-19 vaccine trial (Nov. 18, 2020). The efficacy in adults 65+ years of age was determined to be over 94%, and 9/10 severe cases of COVID-19 were observed in the placebo group.  
  • What that means: The final analysis was based on 170 confirmed cases of symptomatic COVID-19. 162 of those were observed in the placebo group. That means only 8 people became naturally infected with SARS-CoV-2 and developed symptoms after receiving the Pfizer vaccine.

  • Approx. 30,000 enrolled U.S. participants (aged 18+).
  • 37% of participants from communities of color, including more than 6,000 identifying as Hispanic or Latinx and more than 3,000 identifying as Black or African American.
  • 42% of participants from medically high-risk groups (including individuals 65 years of age and older, as well as those with pre-existing/underlying chronic diseases, such as diabetes, severe obesity and cardiac disease). 
  • 94.1% overall efficacy and 100% efficacy against severe disease were reported after the final analysis of Moderna’s Phase 3 COVID-19 vaccine trial (Nov. 30, 2020).
  • What that means: The final analysis was based on 196 confirmed cases of symptomatic COVID-19. 185 of those were observed in the placebo group. That means only 11 people became naturally infected with SARS-CoV-2 and developed symptoms after receiving the Moderna vaccine. Furthermore, 30/30 severe cases were observed in the placebo group, meaning there were zero cases of severe COVID-19 disease in those who were vaccinated. 

  • 43,783 enrolled participants (aged 18+).
  • Trial sites in 8 countries and 3 continents.
  • 44% U.S. participants, of which 74% are white; 15% are Hispanic and/or Latinx; 13% are Black/African American; 6% are Asian and 1% are Native American.
  • 34% of participants over age 60 and 41% of participants with comorbidities associated with increased medical risk.
  • 66% efficacy against moderate to severe disease and 85% efficacy against severe/critical COVID-19 was reported amongst all volunteers (even those infected with circulating SARS-CoV-2 variants) following the interim analysis of J&J’s Phase 3 COVID-19 vaccine trial (Jan. 21, 2021).  
  • What that means: The interim analysis was based on 468 cases of confirmed, symptomatic COVID-19. Because it was conducted after SARS-CoV-2 variants (such as B.1.1.7 and B.1.351) were identified as potential threats to vaccine function, J&J was able to design its trial to test the efficacy against specific variants. 28 days post vaccination, the vaccine was reported to be 72% effective at preventing moderate to severe disease in the U.S., 66% effective in Latin America and 57% effective in South Africa. Publication of the breakdown of the number of cases reported in each geographic region is still pending. There were no COVID-19-related hospitalizations or deaths reported in people who received the J&J vaccine during trial.

Which vaccine is the most effective? 

Direct comparison of the efficacy values of these studies does not account for differences in trial design or the presence of circulating variants during J&J vaccine testing. For example, J&J evaluated how effectively their vaccine prevented combined endpoints of moderate and severe COVID-19, while Pfizer and Moderna evaluated how effectively their vaccines prevented a primary endpoint of symptomatic COVID-19.
However, all 3 vaccines have been shown to not only stimulate antibody production, but also to induce T-cell activity against SARS-CoV-2 and prevent COVID-19. Interestingly, virus specific T-cells, lymphocytes that recognize and eliminate infected cells, have been detected even in cases of SARS-CoV-2 infection that do not appear to generate detectable antibodies. Furthermore, the growing number of COVID-19 vaccines that have been successfully administered provides additional evidence of their safety and efficacy.

Who is evaluating the data from these studies?

An independent Data and Safety Monitoring Board is in charge of evaluating the safety and efficacy of vaccine trials. These committees are composed of people who do not own the company or trials under review, which is important to help ensure that those who stand to profit from the vaccine are not involved in the evaluation of trial data. 

What is an emergency use authorization (EUA)?

It’s important to recognize that EUAs are not the same as FDA approval, but rather a tool that allows the unapproved use of medical products to diagnose, treat or prevent serious or life-threatening disease in times of emergency, and when no other alternatives are available. The FDA has provided guidance for the development and licensure of COVID-19 vaccines, which clearly requires “direct evidence of vaccine safety and efficacy in protecting humans from SARS-CoV-2 infection and/or clinical disease.”

What are the side effects of COVID-19 Vaccines? 

The most commonly reported vaccine side effects include the following:
  • Injection site reactions (pain, redness, swelling).
  • Fatigue.
  • Headache.
  • Muscle and joint pain.
In some cases, nausea and fever have occurred. And rare incidences of anaphylactic reaction have been reported following administration of Moderna (0.0025% or 2.5 cases per 1 M doses), Pfizer (0.0047% or 4.7 cases per 1 M doses) and J&J (2 cases total, as of Feb. 26, 2021). In most cases, these reactions have occurred in individuals with a history of severe allergic reaction.
It’s important to understand that the side effects mentioned above are signs that the immune system is working and not that the vaccine is unsafe for use. No serious, long-term side effects have yet been reported. But this will continue to be closely monitored as more vaccine doses are administered.

What are the key differences between the 3 vaccines?

Viral-vectored vaccines are more stable.

mRNA vaccine development has been historically stunted by engineering challenges because unprotected RNA is environmentally unstable. Enzymes that degrade RNA, called RNases, are found in almost every type of prokaryotic and eukaroyotic cell. In fact, RNases are naturally secreted in human tears, saliva and mucus as a defense against microbial invasion. Fortunately, enveloping mRNA with a lipid nanoparticle coating ensures the genetic messages reach their target cells unscathed.

Viral-vectored vaccines are more stable than mRNA vaccines for multiple reasons. First, DNA is, by nature, more environmentally stable than RNA; and second, the adenovirus shell helps protect the genetic message that is carried inside. As a result, the J&J vaccine can be transported and stored at normal refrigerator temperatures.

mRNA vaccines require ultra-cold storage.

The fragility of RNA makes storage of this type of vaccine significantly more challenging. Basic laboratory protocol calls for unprotected RNA to be stored at -80°C to remain viable. Pfizer’s vaccine candidate requires similar subzero storage temps (-70°C). Unfortunately, many hospitals and treatment centers (especially in rural areas and developing countries) are unequipped and can’t afford to accommodate those requirements. In order to address these concerns, Pfizer has designed its own packaging, which uses dry ice to keep the vaccine cold enough to be stored for a few weeks without the need for specialized freezers. 
Moderna, on the other hand, has announced that its vaccine candidate can remain viable for up to 6 months at -20°C and up to 30 days at normal refrigerator conditions (2-8°C). The difference likely has to do with the way the vaccine is encased. According to an NPR article, which quoted a Moderna spokesperson, the increased durability of the Moderna vaccine is due to its “lipid nanoparticle properties and structure.” Time will tell how each company manages manufacturing, distribution and storage demands. 

Viral-vectored vaccines are less expensive to manufacture.

Viral-vectored vaccines are less expensive to manufacture than mRNA vaccines, a factor that when coupled with J&J’s current single-dose regimen, may be a game changer when it comes to increasing the global supply of COVID-19 vaccines.

mRNA vaccines can be more rapidly produced. 

mRNA vaccines are especially efficient to produce, a factor that has undoubtedly given this platform an advantage during the pandemic. The reason mRNA vaccines can be so quickly engineered is that they're almost entirely synthetic. All researchers really need is the genetic sequence of the desired protein (and a delivery platform). No live virus, culture, eggs or bioreactors required. 

Within 2 months of learning the sequence of the SARS-CoV-2 spike protein, Moderna was able to engineer enough vaccine to begin its first human trials, but this speedy production was not rushed. It is important to understand that COVID-19 vaccines are dependent upon, and made possible by, nearly 17 years of research, which began when SARS-CoV was first identified in 2003, as well as decades of research and development surrounding mRNA technology.  

What other candidates are showing promise? 

There are many additional vaccine candidates in the pipeline, a number of which are showing promise and/or have already received authorization outside of the U.S. Below is a brief introduction to 2 of them. 

Sputnik V

Sputnik V is another adenovirus-based vaccine, developed by a Russian company, known as the Gamaleya Research Institute of Epidemiology and Microbiology. It is unique in that its 2-dose regimen relies on 2 different adenovirus vectors to carry S protein DNA to host cells. Much like J&J, the first dose uses recombinant Ad26, but the second dose uses a recombinant version of Ad5. 
press release announcing that the second interim analysis of trial data showed 91.4% efficacy 28 days after the first dose and 95% efficacy 21 days after the second dose was published on Nov. 23, 2020. At that time, 22,000 participants had received the first dose of vaccine and 19,000 had received the second of the 2-dose regimen. The vaccine was initially criticized for being rolled out prior to the release of final trial data. But in Feb. 2021, Phase 3 trial results indicated a 91.6% efficacy with no unusual side effects, and the vaccine is currently being administered in multiple countries including Russia, Argentina, Belarus, Hungary, Serbia and the United Arab Emirates.


The University of Oxford partnered with AstraZeneca, a British-Swedish multinational pharmaceutical company, to produce another adenovirus-based vaccine using a replication deficient, modified form of chimpanzee adenovirus ChAdOx1 to deliver S protein DNA to host cells.
On Nov. 22, 2020, AstraZeneca, announced that at the interim analysis of its clinical trial the vaccine had an average efficacy of 70%. However, the company simultaneously revealed that there was dosing discrepancy between the testing sites of the trial (United Kingdom and Brazil). In the U.K., 2 different vaccine doses were tested, while the Brazilian site used only one. Unfortunately, this inconsistency caused a range in efficacy from 62%-90%.
Further investigation of clinical trials pointed to an efficacy of 82.4% in patients who received 2 standard doses of the vaccine, and despite some uncertainty, the European Medicines Agency (EMA) and India authorized the vaccine for conditional emergency use. Unfortunately, concerns about reports of blot clots caused many European countries, including Denmark, Norway, Iceland, Ireland, France, Germany and Italy to suspend use of the vaccine in March 2021. AstraZeneca has since issued a statement to update the safety of its vaccine, in which they reported a careful review of available safety data from over 17 million people vaccinated in the European Union (EU) and U.K., with 15 events of deep vein thrombosis (DVT) and 22 events of pulmonary embolism (as of March 8, 2021). The company also stated “This is much lower than would be expected to occur naturally in a general population of this size and is similar across other licensed COVID-19 vaccines.” However, the EMA’s assessment of the risks and benefits of the vaccine is ongoing.

What questions still need to be addressed?

Biology and Immunology

There are a number of questions surrounding front runner COVID-19 vaccine candidates that remain unanswered. Some of these have to do with the biology of the virus and/or host immune system, including how long the vaccine will remain protective. Will boosters be needed?  Scientists are actively researching the immunopathology of SARS-CoV-2, and so far, data about the longevity of immunity look promising. But we still do not know how long the vaccine will remain protective.

Pregnancy and Children

The Phase 3 trials detailed above were conducted on non-pregnant participants, 18 years of age and older. Thorough investigation of the safety and efficacy of these vaccines in pediatric and pregnant populations is still urgently needed. Pfizer and Moderna Phase 2/3 trials are underway, and J&J is planning to conduct similar studies as well.

Vaccine Hesitancy

Another subset of questions has to do with public confidence and vaccine hesitancy. As case numbers continue to ebb and flow across the country, and many are experiencing local surges of SARS-CoV-2, weariness seems to be spreading as quickly as the virus itself. For some, the news of an effective way to prevent further spread of this disease could not come soon enough. For others, particularly those from underrepresented and underserved communities, it is a harbinger of a new kind of uncertainty and unease. Can we trust a vaccine that was developed so quickly? How do we address and prevent the recurrence of historical abuses and vaccine mishandling? 
In order to address these concerns, vaccine researchers and production companies must be open and transparent with their trial data, and scientists must address sources of vaccine hesitancy and misinformation directly. We must be honest about what we do not yet know and work to share the knowledge we do have in a way that empowers everyone to make informed decisions, which promote the health and well-being of ourselves and our communities.

Author: Ashley Hagen, M.S.

Ashley Hagen, M.S.
Ashley Hagen, M.S. is the Science Communications Specialist at the American Society for Microbiology.