Only a limited number of Covid-19 vaccines have been used so far, but hundreds more are still being developed and tested worldwide. Some, such as protein-based vaccines, may eventually prove to be a more effective or appropriate choice for certain populations.

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Which Covid-19 vaccine is the 'best'?

According to STAT News, the world's vaccine supply has largely been made up of shots developed by major pharmaceutical companies such as Pfizer-BioNTech, Moderna, Johnson & Johnson, and AstraZeneca. However, those aren’t the only vaccines available and they may not be the most effective against Covid-19.

Currently, according to STAT News, 128 Covid-19 vaccines are being tested in clinical trials—21 of which have already been authorized for use in general population worldwide. A further 194 vaccines are in preclinical development in labs or are being tested in animals. And with so many potential Covid-19 vaccines still being developed and tested, it is not yet clear which vaccine is the safest, most effective, or most appropriate for certain groups, STAT News reports.

That's especially true considering the variety of factors that need to be considered when judging a vaccine. Factors include the vaccine’s safety and effectiveness across variants; short-, medium-, and long-term immunity; and overall health outcomes. Comprehensive data on these factors is not yet available for all the different Covid-19 vaccines.

The World Health Organization is currently tracking 427 ongoing observational Covid-19 studies to monitor the effectiveness and impact of different vaccines being used worldwide.

Protein-based Covid-19 vaccines may lead to a 'new era' of immunization

Although mRNA and viral-vector Covid-19 vaccines are most common at present, protein-based vaccines may soon become an effective alternative, Nature reports. Protein-based vaccines deliver purified proteins, along with immunity-stimulating adjuvants, directly into a person's cells. This kind of vaccine has been used for decades to protect people against hepatitis, shingles, and other viral infections.

And for a few key reasons, protein-based vaccines appear to be potent players on the overall vaccine playing field against Covid-19 specifically, Nature reports.

1. Comparable efficacy levels

Around 50 protein-based vaccines are currently in clinical testing, and a few have already yielded promising efficacy data. For instance, Novavax reported that its protein-based vaccine was 100% protective against moderate and severe Covid-19 and had an overall efficacy rate of 90.4% in a large-scale trial of 30,000 participants.

In addition, Clover Biopharmaceuticals reported that its protein-based vaccine had a 67% efficacy rate against symptomatic Covid-19 of any severity. Both vaccines also produced antibody levels similar to those produced by mRNA shots, Nature reports.

2. No serious side-effects—and few minor ones

Furthermore, none of protein-based vaccines currently being tested have shown any major side effects. And the minor side-effects commonly reported with mRNA or viral-vector Covid-19 vaccines—such as headaches, fevers, nausea, and chills—have been less common among participants who have received protein-based vaccines.

For example, fewer than 1% of participants who received a protein-based vaccine from Taiwan's Medigen Vaccine Biologics Corporations developed fevers in clinical studies. "The safety profile is very much like those of influenza vaccines," said Szu-Min Hsieh, an infectious disease specialist at the National Taiwan University Hospital, who recently published the vaccine's phase 2 trial results.

Separately, Cindy Gay, an infectious disease physician at the University of North Carolina School of Medicine, who co-led testing of Novavax's vaccine, said the fact that there are fewer side effects associated with protein-based vaccines will "allow a lot of people not to fret as much."

According to Nature, this means vaccinated people who are concerned about side effects from mRNA or other Covid-19 vaccines may seek out protein-based vaccines as boosters when they are available.

3. Variable design

While these protein-based vaccines have some design elements in common, they differ widely on the form of the spike protein they deploy. They range from single proteins to triads, from full-length spike proteins to fragments, etc. And many of these vaccines are manufactured using different types of cells to synthesize the protein.

Notably, those differences means that the success of any one protein-based vaccine doesn't guarantee the success of others. Each protein-based vaccine could have distinct efficacy and safety profiles, according to Thomas Breuer, chief global health officer for GlaxoSmithKline. "I could imagine that you will see differences, but time and the phase [3] trial results will give us the ultimate answer," he said.

But that variability could benefit booster programs. A "mix-and-match" approach to different Covid-19 vaccines has been shown to effectively prevent disease, John Mascola, director of the Vaccine Research Center at the U.S. National Institute of Allergy and Infectious Diseases, said.

4. Inexpensive production requirements

In addition, protein-based vaccines may be an important tool in addressing current vaccine inequity between wealthy and poor nations. Currently, fewer than 6% of people in low-income countries have been vaccinated against Covid-19. Protein-based vaccines are less expensive to produce than mRNA vaccines and can be stored at a broad range of temperatures, which may allow manufacturers in less-wealthy countries to produce and distribute them more easily.

For example, a protein-based vaccine licensed by Biological E, a company based in India, uses yeast as its cell manufacturing system. According to Maria Elena Bottazi, a virologist at Baylor College of Medicine who helped develop the vaccine, the simple manufacturing system "probably [makes the vaccine] the easiest and cheapest to scale" of all the Covid-19 vaccines currently on or near the market.

"The world needs these protein-based vaccines to reach those vulnerable populations," said Nick Jackson, head of programs and innovative technologies at the Coalition for Epidemic Preparedness Innovations. "Protein vaccines are going to beckon in a new era of Covid-19 immunization." (Rea, STAT News, 11/17; Dolgin, Nature, 11/8)