How Delta Is Bolstering the Case for Covid Boosters

(Bloomberg) -- Covid-19 booster shots are being rolled out in the U.S. and other countries in response to waning antibody levels in already vaccinated individuals, and the increased threat posed by the hyper-infectious delta variant of the coronavirus that causes the disease. Giving a third shot to healthy people is a contentious strategy, since many low- and middle-income countries have yet to immunize even a tenth of their population. From a scientific standpoint, though, there’s mounting evidence that it could help stem transmission and avert hospitalizations and deaths.

1. What’s happening to antibodies?

Antibodies are needed to neutralize or block the virus, called SARS-CoV-2, before it can invade the cells lining the nose and throat, where it first replicates to cause an infection. Numerous studies have reported a reduction in antibody levels over the six months following full immunization. But the degree to which that occurs with Covid shots appears to vary depending on factors including:

• The vaccine type and the amount of active ingredient in it
• Prior exposure to the virus, either from a natural infection or a previous shot
• An individual’s immune response, which is influenced by age and pre-existing diseases, especially those that weaken the immune system
• The interval between doses

2. How significant are waning antibodies?

Scientists don’t really know the full implications yet, although waning appears to be a more significant concern among people over 65 years. One reason is that antibodies are only a part of the immune response -- other components also play critical protective roles. For instance, vaccination generates a durable immune memory in most people. So-called memory B cells mature and increase in number over six months, so that if another infection occurs, new antibodies can be made that are better at blocking coronavirus variants. Additionally, high levels of vaccine-induced T cells, a type of white blood cell capable of finding and killing virus-infected cells, can be detected after six months, helping to ward off serious illness. That means that, while a decline in antibody levels over time might result in an increased risk of breakthrough infections, vaccination remains highly effective at protecting against developing a life-threatening case of Covid. In the U.S., hospitalization rates for Covid among adults were about 10-to-22-times higher in the unvaccinated versus vaccinated, the Centers for Disease Control and Prevention said in September.

3. Do booster shots help?

Yes. Data filed by vaccine makers with regulatory authorities, such as the U.S. Food and Drug Administration, indicate an additional vaccination several months after the completion of an initial series results in a substantial increase in levels of protective antibodies that correlate with improved vaccine effectiveness, including against worrisome variants. For example, the administration of a half-strength Moderna Inc. shot at least six months after the second of two standard doses resulted in a 15-times higher level of virus-neutralizing antibodies a month later compared with pre-booster levels. Importantly, antibodies targeting the delta variant jumped 18-fold compared with pre-booster levels. Preliminary findings from a study run by the U.S. National Institutes of Health and presented in October found that booster shots were well-tolerated and that using different types could provide an even greater benefit than receiving another dose of the same brand. That’s one of the reasons the FDA approved a so-called “mix and match” strategy for certain high-risk individuals. 

4. Would boosters stem spread? 

Yes. Higher antibody levels should help prevent the coronavirus from infecting cells and causing an infection. And, if an infection does occur, higher antibody levels should help clear the virus faster, reducing the likelihood of onward transmission. That’s supported by a study that found people infected with the delta variant have fewer viral particles in their upper airway if they had a booster shot than if they hadn’t. While immunizing unvaccinated people, especially in developing countries, would be more effective than providing a third dose to those already vaccinated, the benefit of a booster in reducing transmission could prevent future surges in some populations. Plus, not all breakthrough cases in vaccinated people are mild; a minority of people will come down with a severe illness. People could also develop persistent symptoms or conditions associated with so-called long Covid.

5. Are boosters working in the real world? 

Early data from Israel, one of the first countries to vaccinate widely, is encouraging. It began offering third shots to vulnerable people in July, and gradually expanded the program, after breakthrough infections led to a surge in cases. Numerous studies there indicate boosters curb transmission, severe illness and death. One study found people who received a supplemental dose of the vaccine made by Pfizer Inc. and BioNTech SE had a 48%-to-68% lower risk of infection a week to 13 days later, compared to those who got the standard two-dose regimen. The protection increased with time, with a 70%-to-84% reduced risk of testing positive two weeks to 20 days after getting a third shot. Data presented in October found a boosters were associated with a 3-to-10-fold reduction in the rate of Covid-associated deaths among the elderly. 

6. Why is delta so challenging?

It’s been shown to replicate faster inside the nasal cavity than was observed with previous strains. So an infected person has more virus to transmit to others -- and one or two days sooner, potentially well before developing any symptoms. That makes contact tracing more difficult as well. Delta is also better at evading pre-existing immunity, rendering vaccines less potent. The more the virus circulates, the more opportunity it has to undergo further genetic changes that could give rise to new variants that may be even more pernicious. 

7. Why is it contentious to offer boosters?

Large swaths of people in many nations are yet to receive any Covid vaccine. It’s believed their access will be reduced further with the mass roll out of third doses in better-resourced countries. In some nations, wealthy individuals are obtaining an extra dose while most of their fellow citizens remain unvaccinated. Booster doses in the context of such inequity is like handing out extra life vests to people who already have them, while we’re leaving other people to drown, says Mike Ryan, executive director of the World Health Organization’s health emergencies program. 

8. Are there are other ways of improving protection?

Yes. New vaccines, including variant-targeting inoculations, are in development that may improve protection. Scientists are also studying whether combinations of vaccine types and longer intervals between doses may also yield more robust immune responses. The data so far are encouraging.

The Reference Shelf

• Related QuickTakes on the debate over booster shots, long Covid, the effectiveness of Covid vaccines, mixing vaccines, vaccine nationalism, mRNA vaccines, coronavirus variants, why delta is the most disruptive variant, breakthrough infections, and how these makes the goal of herd immunity harder to reach.
• Bloomberg Intelligence says a new delta variant adds to pressure for boosters.
• Jennifer Juno   and Adam Wheatley  from the Peter Doherty Institute for Infection and Immunity discuss the pros and cons of boosters in Nature.
• An editorial from Bloomberg Opinion on vaccinating the world.

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