More than two years after the pandemic, SARS-CoV-2, the virus that causes COVID-19, continues to challenge us. The ability to mutate rapidly has led to the evolution of increasingly infectious variants that can better hide from our immune response.
Vaccines are a huge achievement of modern science and have played a vital role in mitigating the worst effects of COVID. But are the vaccines we currently have up to the latest COVID variants?
Today’s COVID vaccines are all based on the genetic building blocks, or DNA sequence, of the original ancestral strain of SARS-CoV-2. Most of these vaccines target the spike protein — the part of the virus that attaches to our cells to gain entry.
The vaccines work by allowing our immune cells to mount a targeted response to the spike protein, including generating antibodies known as neutralizing antibodies. These prevent viruses from entering our cells and help other immune cells find and destroy any viral invaders.
But SARS-CoV-2 is a slippery customer and mutates with notable changes in the spike protein. That means those vaccine-induced neutralizing antibodies are less effective than they once were.
Is it time for a new generation of COVID vaccines?
The idea of vaccinating against variants rather than the ancestral strain is gaining popularity. This is not a new concept in vaccine development. For example, our annual flu shots focus on circulating variants.
One approach is to create a so-called “bivalent” vaccine that targets both the spike protein of omicron (BA.1) and the ancestral strain. Moderna is currently testing this option in combined Phase 2 and 3 human trials. Data yet to be peer reviewed suggest that this results in an approximately 2-fold increase in neutralizing antibodies to BA.1, compared to the original COVID vaccines.
Other Moderna studies look at various bivalent combinations, including vaccines targeting the ancestral and beta strains, which show promise.
Pfizer has also released trial data on its booster candidate specifically tailored for BA.1. The company says this reformulation elicited an immune response to BA.1 that was superior to that of the original COVID vaccine.
So should we invest in these new vaccine candidates? The US Food and Drug Administration seems to think so, having approved the use of these ommicron-specific shots later this year.
However, investing in and rolling out new vaccines doesn’t come cheap, and there are important questions to answer. As we know, SARS-CoV-2 is constantly mutating and changing. Less than a year ago, the delta species dominated the world, and before that we had alpha and beta. So are ommicron variants the right ones to target? Will they still be dominant a year from now? We just don’t know.
Even with ommicron species, there is variation. The BA.1 variant targeted by these new vaccine candidates has recently been outcompeted by BA.4 and BA.5† The BA.4 and BA.5 variants are even more resistant to neutralizing antibodies, usually triple or quadruple, than BA.1. So the question is, if omicron gets through, would these omicron BA.1 vaccines work better against BA.4 and BA.5 than the original vaccines? Data yet to be peer reviewed suggests that the bivalent vaccines may be slightly better than the original vaccines.
However, Omicron may be a poor vaccine candidate as recent data show that infection with omicron does not confer robust immunity and is characterized by low levels of neutralizing antibodies, which must be higher and more persistent to prevent rapid reinfection. This could, in large part, explain why so many of us contract COVID multiple times. If we see the same thing with our vaccine-induced immunity to omicron, omicron-specific vaccines may not be a worthwhile investment.
All this does not mean that we should stop looking for long-term protective vaccines. But maybe there is room to focus on different strategies. Two exciting avenues emerge.
The first are vaccines that target other parts of the viral structure that are more stable, or vaccines that target multiple parts of the virus. This may not result in a vaccine that can completely prevent infection, but it may be more durable than current vaccines.
Another way is to take advantage of the ability of neutralizing antibodies in the nose and throat to target SARS-CoV-2 at the point of entry. These antibodies form a barrier that prevents the virus from entering the body, so a vaccine that generates neutralizing antibodies in the nose and throat could stop the virus. Studies testing nasal vaccines look promising, although they are still in the early stages.
Where does this leave us now? An ideal vaccine candidate would elicit long-lived neutralizing antibodies and give us lifelong immunity. Instead, we learned that for COVID, our immune system needs boosters to replenish those neutralizing antibodies and boost the number of memory cells that support immunity.
The last UK-wide booster campaign was in December 2021. Studies had shown that COVID vaccination followed by infection resulted in months of immunity, but this was before ommicron, which we now know does not produce robust immunity. Against ommicron, many of us will have minimal neutralizing antibodies left.
With the high probability of another variant in the fall, in addition to the fear of a bad flu season, it seems wise to start a fall booster campaign with a much broader coverage than the spring campaign. This means targeting not only the over-65s and others at higher risk, as currently planned, but also younger age groups.
It is critical that we reach those who are not fully vaccinated, so any campaign should include targeted community education. This should also happen alongside other risk mitigation strategies, such as wearing masks, to keep us safe and enable us to live with COVID.
Should You Get a COVID-19 Booster Shot Now or Wait Until Fall? Two immunologists help weigh the options
Provided by The Conversation
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