The Impact of Seasonal Coronaviruses on the COVID-19 Vaccination Strategy in the United States from 2022 to 2023
The picture became clearer in 2022, with the Omicron BA.1 variant causing large epidemics. There was an increase of immunity within populations and a decline in transmission but only for a new subvariant, BA.2, which was less effective. Large epidemics followed and the cycle started again, with another cycle in mid-2022 when BA.5 emerged.
This pattern will be seen in 2023 and beyond if this evolutionary trajectory continues. It is a similar dynamic to the seasonal coronaviruses that have been causing epidemics for decades. A 2021 study by researchers at Fred Hutchinson Cancer Research Center found that coronaviruses gradually evolve over time, so prior immunity is less effective.
The prediction challenge is likely to be a regular occurrence for Covid. Some countries have already approved shots that are adapted for the Omicron BA.1 subvariant. Can these vaccines match the variant that circulates further down the line? Decisions for winter 2023–24 in the northern hemisphere will likely have to be made in early 2023. Getting the choice right could have major implications for the size and severity of future Covid waves. The H3N2 influenza subtype, which tends to cause the largest seasonal epidemics, has an effectiveness against symptomatic disease of less than 50 percent.
At the same meeting, the vaccine advisory panel unanimously endorsed the agency’s proposal to adopt a single COVID-19 vaccination composition for primary and booster doses. Currently, people in the United States complete a primary COVID-19 vaccination series — at least two doses of the vaccines made by Pfizer–BioNTech, Moderna or Novavax, or a single jab of a Johnson & Johnson vaccine — all of which should then be followed by a booster two months later. The original vaccine from Pfizer-bioNTech and Moderna was initially offered an extra dose, but now only one strain of the same disease is included in the booster.
“We desperately need to simplify the vaccination schedule,” says Megan Ranney, a physician and public-health specialist at Brown University in Providence, Rhode Island. “If we’re going to sustain our ability to vaccinate the country, we have to move toward a more standardized schedule, from a behavioural-science point of view.” The proposal to standardize the vaccine composition for the whole series would alleviate some of the confusion, and it could boost vaccine compliance because it would offer both jabs and the yearly flu vaccine. “These changes make a lot of sense.”
Uptake of bivalent boosters has been low in the United States: about 15% of eligible people have received a two-strain jab. Some experts say that is because many people have received a mixture of vaccines, which has led to confusion over which type of booster they should get and when.
Standardizing vaccine composition for the primary and booster series would probably mean that the bivalent vaccine would become the main formulation for people who haven’t yet had a primary series.
The bivalent boosters currently used in the United States, the United Kingdom and elsewhere target both the strain circulating at the start of the disease and an Omicron strain. Data shared at the meeting show that people who get a single booster are more likely to die from COVID-19 than people who get a bivalent booster. However, any booster still reduces overall chances of death from COVID-19.
In a word: evolution. The first approved COVID-19 vaccines were tested for protection against versions of SARS-CoV-2 that had not changed much since the virus was first identified. These vaccines come in different types — some are composed of messenger RNA, others are inactivated versions of the coronavirus itself or some of its proteins — but all work by exposing the body to antigens (portions of the virus) to provoke an immune response without causing disease.
The spike Protein is a target for B cells. T cells that destroy infections can recognize many other diseases. For this reason, vaccines that deliver other proteins could help protect people whose immune systems do not generate strong antibody responses. Such vaccines might also be more resilient to viral evolution, because non-spike proteins tend to vary less between variants.
The vaccines work in many ways. Like other COVID-19 booster shots, they stimulate the memory B cells already established by previous vaccines; some of this cellular response leads to antibodies that can recognize Omicron. The pool of B cells that produce the antibodies that bind more tightly to Omicron’s spike can strengthen over time. New B cells that can produce their own vaccines are recruited by the Omicron components of bivalent vaccines.
These effects might mean that a bivalent booster provides better protection against Omicron than does a booster dose of the original vaccine. But it’s still unclear how substantial that advantage is in practice.
The goal of some of these vaccines is to generate an immune response against particular regions of the spike protein that are conserved across SARS-CoV-2 variants and some related coronavirus species, meaning that they tend not to mutate in new variants. TheRBD is a region of interest due to the fact that itbinds to the ACE2 receptor in human cells and is attacked by some of the most potent infections-blocking antibodies.
When a B cell recognizes more than one RBD on these mosaic nanoparticles — latching on to conserved regions from multiple virus species — it binds strongly. This, in turn, triggers that B cell to multiply and produce more antibodies (as well as memory B cells to fight future infections). B cells that recognize an RBD from just one viral species bind weakly, and do not generate this response. The scientists hope that using mosaic nanoparticles will result in an enriched pool of anti- coronaviruses that can recognize multipleRBDs.
The US biotechnology company Gritstone is developing one such vaccine: it delivers instructions for several SARS-CoV-2 proteins using mRNA vaccine technology. Vaxxinity is trying to make a vaccine that will expose the body to more than one antigens. The company says it plans to apply for UK and Australian authorization this year, after a phase III trial showed the vaccine was safe and prompted a strong antibody response when used as a booster.
This means that a smaller — and potentially cheaper — dose of saRNA vaccines could achieve the same or even a stronger immune response, compared with conventional mRNA vaccines. A smaller initial dose might also reduce side effects.
The company has begun another phase III trial in Japan which it says could lead to an application for authorization in that country. Gritstone is using saRNA technology to deliver additional SARS-CoV-2 proteins in a candidate T-cell vaccine that has completed a phase I trial.
A team led by researchers at the US Walter Reed Army Institute of Research in Silver Spring, Maryland, is developing another protein nanoparticle vaccine, using an iron-carrying protein called ferritin. This self-assembles into a spherical particle, and is then studded with the full SARS-CoV-2 spike protein. It is being tested in an early stage.
However, the South Korean company developing the vaccine, SK biosciences, said in late 2022 that it had paused production amid low demand for the vaccine in South Korea.
Some COVID-19 vaccines are inhaled as a mist through the nose or mouth, or as nasal drops. By prompting immune responses at the point where SARS-CoV-2 enters the body — in the thin mucous membranes that line the nose and mouth — these vaccines could, in theory, stop the virus before it spreads.
Data from animal studies suggest this might be possible, and at least five nasal vaccines have already been approved for use — two in China and one each in India, Iran and Russia. There is no data yet as to whether these vaccines are better than injections at cutting down infections or transmission.
Melanie Saville, executive director of vaccine research and development at the Coalition for Epidemic Preparedness Innovations (CEPI), says that the biggest challenge to development of next-generation COVID-19 vaccines is proving they offer genuine improvements over existing jabs.