In-Depth: The four leading COVID booster shot strategies

Posted at 9:33 AM, Apr 26, 2021
and last updated 2021-04-27 00:38:04-04

SAN DIEGO (KGTV) -- Amid the threat of variants, vaccine makers are testing a range of strategies to boost immunity, from targeted recipes to the cocktail approach found in the flu vaccine.

All of the vaccines authorized in the U.S. are effective against severe COVID-19, but research suggests they are somewhat less effective against certain variants -- particularly the variant first discovered in South Africa.

Pfizer, Moderna and Johnson & Johnson are responding by developing booster shots, but in some cases they’re exploring different approaches.

The “basic booster”

All of the vaccine makers are testing a “basic booster.” This is the exact same formula given one extra time; a third shot in the case of Pfizer and Moderna, or a second shot of J & J.

“That has the advantage of simplicity,” said Dr. Alessandro Sette, an immunologist at the La Jolla Institute for Immunology.

The basic booster is the easiest to test and manufacture, Dr. Sette said, and the concept is to defeat variants by sheer strength in numbers.

The original vaccine recipes produce antibodies that recognize the variants -- they just produce fewer of them. By growing more antibodies overall, the theory is that you will also increase the number that can attack the variants. Pfizer estimates a third shot will increase antibody levels 10 to 20 fold overall.

“Basically you can stop the virus by starting your immunity at a much higher level. And you're still safe, even though the antibodies do not work as well against the virus,” Dr. Sette said.

Timing that booster dose will be key, said Dr. John Bradley of Rady Children’s Hospital.

“There is a theoretical possibility that if I get a booster of that same vaccine, especially within a fairly short period of time, I’ll have an even stronger reaction,” he said.

Moderna and Pfizer are experimenting with boosters given 6 to 12 months after the initial doses. Johnson & Johnson is testing boosters at 6, 12, or 24-month intervals.

Strain-adapted vaccine

The second strategy is called a strain-adapted vaccine. This is when scientists come up with a new recipe specifically tailored for a variant.

“The fact that we can take an mRNA vaccine and just immediately reprogram it with a new variant is an interesting concept and I think is one of the major innovations in terms of vaccine development,” said Dr. Christian Ramers of Family Health Centers of San Diego.

Pfizer, Moderna and Johnson & Johnson are working on shots with recipes tailored to the spike protein in the South Africa variant.

Targeting this particular variant may cast a wide enough net to block other variants as well, according to research released Wednesday in the New England Journal of Medicine. Researchers found that antibodies generated after infection with the South Africa variant also efficiently blocked the original virus and the P.1 variant from Brazil.

But what if a different variant sweeps through a country, like the emerging “Double Mutant” in India?

Multivalent booster

Moderna and J & J plan to test a third strategy called a multivalent booster. This approach blends the original vaccine with one or more recipes updated for variants. Moderna is planning to blend its original vaccine with the version updated for the South Africa variant.

“That’s what we get for influenza each year,” said Dr. Bradley. “Influenza mutates and so we need new vaccines each year. And what we do is we pick the most prevalent strains that are likely to circulate, and we put those in the current vaccine for that upcoming season.”

The influenza vaccine is a cocktail of four strains.

The downside to a multivalent booster is the shot can be more complicated to test and manufacture. For now, Pfizer is not planning to pursue a multivalent strategy.

Multiple proteins: the “spike plus” approach

The fourth strategy is the most experimental and probably the farthest off, what Dr. Sette calls the “spike plus” approach.

“Spike is really the best target for neutralizing antibodies, but there are several other proteins” in the virus, he said.

Some companies, like Gritstone Oncology in California, want to make a vaccine that goes after multiple targets on the virus, not just the spike protein that all of the current shots are based on.

“Other parts of the virus may be less easy for a virus to mutate,” Dr. Sette said.

This approach may also produce a more robust T cell response, he said.

Pfizer, Moderna and Johnson & Johnson are hoping to have the first booster shots authorized and ready by the summer -- in case they’re needed.