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COVID-19 Vaccine: Will It Protect Against New Variants And Do You Need A 2nd Dose?

Southern Californians celebrate at a mass vaccination site in Disneyland's parking lot in January. CDC head Dr. Rochelle Walensky cautions that for strongest immunity, recipients get both doses of the Pfizer or of the Moderna vaccine according to schedule.
Southern Californians celebrate at a mass vaccination site in Disneyland's parking lot in January. CDC head Dr. Rochelle Walensky cautions that for strongest immunity, recipients get both doses of the Pfizer or of the Moderna vaccine according to schedule.

As the virus that causes COVID-19 continues its global attack, it has done what scientists predicted it would do — it has given rise to new, slightly different strains. How significant some of those strains will be to the pandemic is now under intense study. Meanwhile, demand for the currently available vaccines is outstripping the early supply, and some scientists have sparked controversy by suggesting holding off on booster shots until more people have had their initial shots. That's something the Centers for Disease Control and Prevention does not endorse — but the agency has extended the timing on the second dose a bit.

What does this all mean for you? Let's start with the question of second doses.

Why do the manufacturers and CDC advise two doses of the Pfizer and Moderna vaccines?

Simply put, because that's what was tested — Pfizer BioNTech went for a 21-day interval in its large trial, and Moderna went for 28 days. The companies wanted the highest chance of success; while a one-dose shot would be easier to administer, two-shot vaccinations offered the insurance that if the first shot wasn't enough, the second one could finish the job. It's the two-jab immunization that has been shown to be 94% or 95% effective in preventing symptoms of COVID-19.

How protective one dose of these vaccines would be over the long run remains unknown. A Moderna spokesperson told The Hill in late December that it expected the double dose would produce the most durable immunity and was not considering a trial of a single dose.

How does my protection build after the first shot and after the second?

The two vaccines currently authorized in the U.S. — Moderna's and Pfizer's — are based on helping your immune system recognize certain proteins in the virus's outer coat. "That stimulates the immune system to make antibodies, and it also stimulates other parts of your immune system," says Gigi Gronvall, an immunologist with the Johns Hopkins Center for Health Security. Those protective antibodies are relatively easy to measure in blood samples, and studies have shown them increasing in quantity a week or so after someone gets their first dose of vaccine. A week or more after the second dose the level of protective antibodies peaks and then falls off only slightly over four months. How long they last beyond that is under study.

But another part of the immune response — a longer-term response — is much harder to measure. Not much is known yet about when that type of immune protection kicks in or when, if ever, it disappears. Infectious disease specialists think this second part of immunity could prove to be important in providing long-term protection against reinfection. They just don't have a lot of data on that yet.

What would happen if I stretched the time period between doses? Would that reduce the vaccine's protection?

While the studies looked at the effect of a strict 21-day interval (for the Pfizer vaccine) before getting the second shot and a 28-day interval for Moderna's, immunologists say there's a bit of wiggle room, judging from experience with other vaccines. At a White House press conference last week, new CDC head Dr. Rochelle Walensky said, "We also know that life can get in the way — that some of those doses may be missed. ... In these rare circumstances, the second dose may be given up to six weeks or 42 days after the first."

In an effort to get more people vaccinated, the United Kingdom's National Health Service is allowing for a 12-week gap between doses for the Pfizer and Moderna vaccines, but the CDC strongly urges not going beyond a six-week interval.

If there's some immune protection gained after the first dose, why should I bother getting the second jab?

This question greatly concerns vaccine experts. They worry that because the vaccine sometimes causes temporary redness, discomfort or brief fever, some people will not show up for their second dose. Remember that with the Pfizer-BioNTech vaccine, a study published in The New England Journal of Medicine in December found that protection didn't start until 12 days after the first shot, reaching 52% effectiveness a few weeks later. Participants then got their second shot — so whether that 52% effectiveness would have worn away if they hadn't got the second dose is unknown. What is known is that a week after the second vaccination, the effectiveness rate hit 95%.

And in its application for emergency use authorization in the U.S., Moderna reported a protection rate of 51% two weeks after the first immunization and 94% two weeks after the second dose.

By definition, that means 94 or 95 out of every 100 people fully vaccinated with both doses of these vaccines can be expected to not get sick with COVID-19 symptoms when they run into the most common version of the virus, but it likely takes both doses to reach that level of effectiveness. In early January, the U.S. Food and Drug Administration reiterated that changing course and going to a single dose now — i.e. skipping the second dose for several months, until many more people have had a chance to get a first shot — would be "premature and not rooted solidly in the available evidence." The agency renewed its strong recommendation that the two-dose schedule be followed.

Is it OK if my second dose comes from a different manufacturer?

No one has tested this sort of mixing and matching of the Pfizer and Moderna vaccines. That lack of testing makes virologist John Moore at Weill Cornell Medical College a little unhappy. But, he says, "the two vaccines are sufficiently similar that there's no reason to doubt that that would still work and be safe."

The CDC says every effort should be made to get the same vaccine in both jabs, but the agency's guidance also allows for a switch between the Pfizer and Moderna products "in exceptional situations in which the first-dose vaccine product cannot be determined or is no longer available." Several vaccines based on different technologies are coming down the line soon; scientists are more hesitant about mixing and matching with those vaccines until tests are done to see how well that works.

I'm hearing about different variants, or strains, popping up. Will the current vaccines protect me from them?

Important new strains of the SARS-CoV-2 virus — the "variants" you're hearing about — have been identified in the United Kingdom (B.1.1.7), Brazil (P.1) and South Africa (B.1.351), and all three have now been found in the U.S. as well. Those variants are more infectious than the original strain, and researchers in the U.K. have said B.1.1.7 may be more frequently lethal.

Scientists' concern right now is mostly with the P.1 variant. It has a particularly worrying cluster of mutations that allow the virus to spread more quickly and help it evade the immune system, which might make it easier for people who have already had COVID-19 (and so have developed some immunity) to still be vulnerable to reinfection with this new strain.

Early investigations are suggesting the current vaccines, as well as Johnson & Johnson's candidate vaccine (not yet authorized for use), may be somewhat less effective against some of the new variants, in terms of preventing all symptoms. But even against the variants, the vaccines do prevent a lot of mild and moderate cases, the data gathered so far suggest, and are very effective, health officials say, against preventing severe cases, hospitalizations and deaths.

Viruses like SARS-CoV-2 mutate all the time, notes Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, and that's another reason to get people fully immunized as quickly as possible.

"Viruses cannot mutate if they can't replicate," Fauci said Monday at a press conference by the White House's COVID-19 response team. "If you stop their replication by vaccinating widely ... not only are you going to protect individuals from getting disease, but you are going to prevent the emergence of variants."

Given these new variants, is there anything I can do to improve my chances of avoiding COVID-19?

Sure. Fauci and Walensky, the CDC's chief, both recommend getting immunized with one of the vaccines authorized in the U.S. as soon as you are eligible — widespread vaccination will very likely help stop the spread of whatever strains of the coronavirus are circulating in your area and lessen the development of new mutations and strains.

And continue to keep your distance from people outside your household, wear a mask, and avoid travel and crowds even after you're fully vaccinated, until the level of virus spreading in your community and any place you go is very low.

I've been hearing about new vaccines nearing FDA authorization. What's coming and should I wait for them?

Don't wait, all those in the know advise. Take whatever vaccine comes your way when you are eligible. All vaccines authorized for use in the U.S. will be very effective; they are just made via different technologies.

Last week, preliminary research results on the effectiveness of two more candidate vaccines were announced — one from Johnson & Johnson's Janssen subsidiary and another from the biotech company Novavax.

Johnson & Johnson's single-dose vaccine is a bit of SARS-CoV-2 genetic material hooked onto a harmless virus. It has been tested in the U.S., Brazil and South Africa, and, according to the company's report of its data, seems to be slightly less effective than the Moderna and Pfizer vaccines in preventing all symptoms of COVID-19, but is highly effective in preventing hospitalization and death from the illness. "When one looks at potential impact on severe disease, it's 85% percent [effective]," Fauci notes, adding, "There are many people who'd rather have the convenience of a single dose."

The J&J vaccine also can be transported and kept for long periods of time at refrigerator temperatures — it doesn't require the deep-freeze storage the Moderna and Pfizer vaccines need. Dr. Paul Stoffels, chief scientific officer at Johnson & Johnson, told NPR last week that his company will apply to the FDA for emergency use authorization in the U.S. this week.

A different candidate vaccine — one from the biotech firm Novavax — is a little further back in completing its clinical testing and consists of a bit of protein from SARS-CoV-2's outer coat. Last week, the company announced that preliminary evidence from studies in the U.K. indicate the Novavax product is nearly 90% effective, suggesting it can handle the B.1.1.7 variant now prevalent there. But in a separate, smaller part of the study — in South Africa, where 90% of the recorded cases were likely due to the troublesome variant B.1.351 — the effectiveness of the Novavax candidate vaccine in preventing all symptoms was a lower 49%.

Meanwhile, Pfizer and Moderna are both actively working on ways to incorporate added protection against the new variants into their existing vaccines.

That pattern of developing and tweaking existing vaccines as more is learned is actually the usual strategy in stopping the spread of infections, public health officials note.

At a recent NPR/Harvard forum, immunologist Barry Bloom of the Harvard T.H. Chan School of Public Health noted that the history of vaccine manufacture back to smallpox is one that follows continual tinkering and frequent improvements on an initial vaccine before the virus is finally squelched in a big population. "I don't think the virus is going to win this war," Bloom says.

How soon might these updated vaccines be available?

Bloom estimates that coming up with a new version of the Pfizer and Moderna products — one that is targeted against problematic variants — would only take about six to eight weeks. After that, of course, it would have to be tested and go through FDA evaluation. Dr. Jesse Goodman, a former FDA chief scientist and now at Georgetown University, notes that the regulatory review could actually go quite quickly if the new vaccines that are developed are essentially the same as the older version, with just a new bit of RNA added. "You might not need the months of placebo-controlled trials" in that case, he says.

Health officials say the process of staying ahead of COVID-19 may eventually prove to be more like what we're used to seeing with the flu vaccine — where the mix of strains addressed by an annual vaccination is tweaked each year to reflect the predominant strains circulating that season. In that same way, people may eventually be advised to get an annual COVID-19 shot, as well as an annual flu shot.

Should I wait on vaccination until I can get one of those updated shots?

Definitely not. Vaccine experts are clear about the need for us all to get fully immunized as soon as we're eligible this year. "We need to vaccinate as many people as we can as quickly as we can," says Fauci. That will help prevent further dangerous mutations and strains from arising.

It seems like the public health advice and what's known about COVID-19 changes every day. How do I know what's trustworthy?

It might help to think of COVID-19 science as developing rather than changing — accumulating knowledge can lead to better ways to fight the pandemic. "As science evolves, the application of that new information will too, and there could be changes in the recommendations," says Dr. Bruce Gellin, president of global vaccination at the Sabin Vaccine Institute. The recent discoveries of variants did not surprise scientists, nor did the slight differences in effectiveness among the new vaccines.

Remember, SARS-CoV-2 is still a very new virus, and more is being learned every day. The CDC's website is now being updated regularly, so that's one good place to check for the latest guidance. Or watch this space for updates.

Joanne Silberner, a former health policy correspondent for NPR, is a freelance journalist living in Seattle.

Copyright 2021 NPR. To see more, visit https://www.npr.org.