The Most Promising COVID-19 Vaccines

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Close-up of potential Covid-19 vaccines in vials in scientist's hands during research and development in laboratory

The COVID-19 pandemic has been a moving target since the day it started—March 11, 2020. Yet efforts to prevent infection and save lives began weeks earlier. Vaccination has proven very effective at combating serious infectious diseases for the past 60 years.

Once scientists identified SARS-CoV-2—the cause of COVID-19—many biotechnology companies and vaccine makers already had the technology to create a vaccine that would guard against it. The hope was a vaccine that would prevent serious illness, hospitalization, and death.

Learn about the most promising COVID-19 vaccines in the United States, including the Pfizer-BioNTech, Moderna, and Johnson & Johnson vaccines, their relative effectiveness, and other vaccines in the pipeline.

Pfizer-BioNTech COVID-19 Vaccine

In November 2020, Pfizer-BioNTech announced the results of an independent analysis of their BNT162b2 vaccine phase III trial that showed it is safe and 95% effective in preventing COVID-19 (the vaccine reduced the risk of COVID-19 by 95%). [In June 2020, the U.S. Food and Drug Administration (FDA) told drug makers the threshold is 50% effectiveness.] The vaccine is 90% effective in "real-world" conditions; that is, in people who were vaccinated outside of the clinical trial. The FDA authorized the Pfizer-BioNTech vaccine for emergency use (EUA) in December 2020. The EUA was extended to ages 12 to 15 in May 2021. The FDA gave full approval for ages 16 and older in August 2021.

The Pfizer-BioNTech vaccine uses genetic material known as messenger RNA (mRNA) encoding the virus's spike protein (S protein) to stimulate the immune system against the novel coronavirus. The upper limit of how long immunity will last is not clear. Research suggests protection from COVID-19 could last a year or longer. However, variants of SARS-CoV-2, including the COVID-19 Delta variant, have mutations in the S protein that can blunt vaccine effectiveness. Studies also show that antibody levels in vaccinated individuals are declining with time. This information, along with increasing infections in vaccinated people, led the FDA to authorize a booster shot for those who received the Pfizer vaccine eight months prior. A boost shot further stimulates the immune system to make antibodies. The hope is that it will help curb rising infection rates among the vaccinated.

Moderna COVID-19 Vaccine

Moderna also uses mRNA in its vaccine. The vaccine, mRNA-1273, is a joint project between Moderna and the NIAID (National Institute of Allergy and Infectious Diseases). It entered phase I trials back in May 2020 and quickly moved through phase II and III trials.

The Moderna mRNA-1273 vaccine was shown to 94.5% effective at preventing COVID-19 in the phase III clinical trial with 30,000 volunteers. Of the 95 cases of COVID-19, 90 occurred in the placebo group and 5 occurred in the mRNA-1273 group. The 11 severe cases occurred in the placebo group. The Moderna vaccine is 90% effective in real-world conditions. The Moderna vaccine received an EUA in December 2020 for people age 18 and older; full FDA approval is anticipated in fall of 2021.

Like the Pfizer-BioNTech vaccine, the Moderna vaccine is less effective against the Delta variant, although both vaccines offer good protection from COVID-19 hospitalization and death. The FDA has also authorized a Moderna booster shot, starting with people who were part of the first phase of COVID-19 vaccination.

Johnson & Johnson COVID-19 Vaccine

Janssen—part of Johnson & Johnson (J&J)—uses the S protein gene in an inactivated cold virus to make their vaccine candidate Ad26.COV2.S. It’s the same technology in their Ebola vaccine currently in use in the Democratic Republic of Congo. Unlike the other vaccines, the Janssen vaccine requires only one dose and can be stored in a standard refrigerator.

Janssen started phase I/II trials in June 2020 and began a large phase III trial with 40,000 participants in September 2020. Phase III clinical trials in humans showed the vaccine was safe and, overall, 66% effective in preventing moderate to severe COVID-19 after the single-dose vaccination. The vaccine was 85% effective in preventing severe COVID-19 and complications requiring hospitalization in people infected with the original virus. However, this vaccine is also less effective against the Delta variant.

FDA authorized the vaccine in February 2021 for people ages 18 and older. The FDA also authorized a booster dose of the J&J vaccine. People who received the J&J vaccine can get a booster shot of the J&J vaccine or the Moderna or Pfizer vaccine.

AstraZeneca and Oxford Vaccine

The AZD1222 vaccine (Vaxzevria) also uses the coronavirus S protein gene in an inactivated common cold virus to stimulate the immune system. Based on its U.S. phase III clinical trial, the vaccine is 76% effective.

The U.K. authorized the vaccine for emergency use based on prior phase III trials in the U.K. and other countries. Dozens of other countries are also administering the AstraZeneca vaccine, but the U.S. has not authorized it for emergency use. Similar to the Janssen/J&J COVID-19 vaccine, there is a link between life-threatening blood clots occurring within two weeks of AZD1222 vaccination, as reported by the European Medicines Agency (equivalent to the U.S. FDA). This adverse event is very rare, but some cases have been fatal.

The AstraZeneca/Oxford vaccine only requires refrigeration for storage and costs less than other vaccines.

Sanofi and GlaxoSmithKline COVID-19 Vaccine

GlaxoSmithKline (GSK) is the world’s largest vaccine maker. It teamed up with another vaccine giant, Sanofi, to make a COVID-19 vaccine. They are behind the other top contenders as far as time goes. What they lack in time compared to the others, they may make up in potency. Their candidate is a viral protein-based vaccine with a vaccine adjuvant, similar to the annual flu shot. The adjuvant essentially enhances the immune response. The idea is to make a stronger vaccine called an adjuvanted vaccine. A stronger immune response could lead to herd immunity sooner.

Importantly, Sanofi-GSK is testing two different vaccine formulations: One vaccine targets the older, more common circulating SARS-CoV-2 strain; the other targets a variant (B.1.351, or Beta) that originated in South Africa.

Sanofi-GSK partnered with the U.S. government and received $2.1 billion for manufacturing funding. Like other such agreements, this one guarantees 100 million doses for the United States. Sanofi has also made deals with the European Union, Canada, and COVAX, an international coalition to provide equitable worldwide distribution of COVID-19 vaccines.

Novavax COVID-19 Vaccine

Novavax's vaccine, NVX-CoV2373, is also an adjuvanted protein-based vaccine using the company's proprietary saponin-based adjuvant. Vaccination requires two doses spaced 21 days apart.

In Novavax's U.S. and Mexico phase III clinical trial, with about 30,000 participants ages 18 and older, the vaccine was 90% effective against COVID-19 and 100% effective against moderate and severe COVID-19. There were 77 total cases of symptomatic COVID-19: 63 in the placebo group and 14 in the vaccine group, all of which were mild. Common vaccine side effects included injection site pain, headache, muscle pain, and fatigue.

The trial was conducted at a time when the most common circulating SARS-CoV-2 strain in the U.S. was the B.1.1.7, or Alpha variant. Results from an earlier phase III trial showed the vaccine was 96% effective against moderate and severe COVID-19 caused by the original virus strain and 86% against the Alpha variant. The vaccine was only about 49% effective against the Beta variant.

Although a booster dose (see below) of the Novavax vaccine increased the level of antibodies that target the Delta variant, the company has not released data on vaccine effectiveness against moderate and severe COVID-19 caused by the Delta variant.

Novavax has submitted findings to the World Health Organization for emergency use listing of its vaccine.

Novavax booster dose

Novavax initiated a new trial in the U.S. and Australia, testing the safety and effectiveness of a booster dose six months after participants finished the two-dose vaccination schedule. Early results show that spike protein antibody levels were about six times higher after the six-month booster than after the primary vaccination regimen. In laboratory experiments, antibodies from trial participant sera were able to block (neutralize) the Alpha, Beta and Delta variant viruses. This suggests the vaccine will provide broad immunity.

Novavax has an agreement with the U.S. government to provide 100 million doses upon its EUA. A trial involving younger people is ongoing.

Other COVID-19 Vaccines

Here are some of the other candidates in the works in the United States and around the world:

  • CureVac is working with GlaxoSmithKline on a "next generation" mRNA vaccine to help combat multiple COVID-19 variants in one vaccine. They hope it will be ready to market in 2022.
  • Imperial College London is formulating vaccines with the ability to rapidly respond to new and future strains of the COVID-19 virus.
  • Medicago and GlaxoSmithKline (GSK) began a phase II/III trial of a plant-derived coronavirus vaccine. Early results show the vaccine triggers a good immune response. Antibodies from vaccinated individuals were 10 times stronger than those from people recovering from COVID-19.
  • Sanofi and GSK started their S-protein vaccine in clinical trials and hope to have a licensed vaccine soon. They are also studying the vaccine as a booster in people previously vaccinated by other vaccines. Sanofi has a second vaccine in clinical trials, in partnership with Translate Bio.
  • Symvivo is currently in clinical trials of its oral (pill) vaccine candidate, which is created with probiotic bacteria.
  • Vaxart started clinical trials with its oral COVID-19 vaccine. Vaxart's later start to clinical trials has allowed the company to re-engineer their vaccine to potentially make it protective against emerging COVID-19 strains.
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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2020 Nov 9
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