A vaccine against the coronavirus may not be as simple as one jab and you’re immune.

There’s a high likelihood an eventual vaccine will require a two-dose series, a month or so apart, with the possibility of a booster several years later, adding to the complexity and cost of administration and distribution.

Much remains unknown about SARS-CoV-2, the virus that causes COVID-19. Even as physicians scramble to understand the natural history of the disease, scientists around the world are working to find vaccines to protect humanity against the virus. Only now are some of the broad outlines of what immunizations might look like becoming clear.

The two doses are likely to be required because SARS-CoV-2 is a newly emerged virus that no one has developed antibodies against. Also, with many potential vaccines being created using new systems it’s believed two doses will be required for full immunity.

The first shot would prime the immune system, helping it recognize the virus. The second shot would strengthen the immune response.

Of the more than 100 vaccine candidates in various stages of testing, almost all are expected to be a two-dose regime, said Barry Bloom, an immunologist and professor of public health at the Harvard T.H. Chan School of Public Health in Boston.

“As far as I am aware, with one set of exceptions, all the front-line vaccine developers are contemplating two shots,” he said. “The one exception is Merck, which last week pushed forward on two vaccines, each of which they hoped would be one-shot vaccines.”

Game on: In the race for a coronavirus vaccine, can Operation Warp Speed avoid politics?

The exact dosing will become clear as potential vaccines reach human clinical trials, said Dr. Kelly Moore, associate director of immunization education for the Immunization Action Coalition.

“The answer is to be found in the human studies that will show how we respond to the vaccine,” she said. “Phase 1 studies look at both dose size and, if animal studies suggest two doses might be needed, then they also look at one dose versus two doses.”

Any coronavirus vaccine that requires two doses will probably need to be given about a month or two apart, though that’s still being worked out, said L.J. Tan, chief strategy officer with the Immunization Action Coalition and co-chair of the National Adult Immunization Summit and National Influenza Vaccine Summit.

When the first dose of a vaccine is given, the immune system reacts to something it hasn’t seen before.

“The immune system looks at it and it processes and remembers it, developing antibodies and immune cells,” which takes about 14 days, said Tan. “If an infection comes at that point you’ll fight it off and you won’t get sick – you’ll be immune.” 

With some pathogens, however, a second dose is necessary to get the immune system fully primed to fight off an infection. 

The latest: Fauci says he’s optimistic about coronavirus vaccine protection but concerned how long it will last

Vaccines series are common

Another unknown is whether one round of inoculations will be enough.

Some vaccines like measles, make a person immune for life. That’s in part because the measles virus is stable and doesn’t change.

A disease like influenza, which is actually comes from multiple strains of flu that continually mutate and sometimes recombine, require updated vaccines every year.

So far, it appears SARS-CoV-2 is relatively stable, indicatingvaccines that protect initially likely will be able to serve as boosters to maintain immunity for longer, said Bloom.

However, a person’s antibody response might lessen over several years. With Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), viruses similar to SARS-CoV-2, some data shows antibody levels decline with time.

“The MERS serology data suggest that by about three years it could fade,” said Dr. Kathryn Edwards, a professor of pediatrics at Vanderbilt University and scientific director of the Vanderbilt Vaccine Research program.

Whether the same will be true of SARS-CoV-2 isn’t yet known. If it is, a booster injection might be needed after a couple of years. “Only testing will tell,” said Edwards.

In the common coronaviruses that cause the common cold, immunity tends to last from three to six months to almost always less than a year, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in an interview with the editor of the Journal of the American Medical Association on Tuesday.

“It may be completely different with this coronavirus, with SARS-CoV-2, it may be that they induce a response that’s quite durable. But it if acts like other common coronaviruses, it’s not likely going to be a very long duration of immunity,” he said.

The front of the line: When a coronavirus vaccine is developed, who will be first in line to get it? A CDC panel usually decides

Double-dose challenges

But there may be no way around a two-dose regime, which is common for many immunizations given to children.

Measles vaccine comes in two doses. The pneumococcal vaccine, which prevents some types of pneumonia, meningitis and the potentially deadly blood infection sepsis, comes in four doses. The DTaP vaccine, which prevents three deadly diseases, tetanus, diphtheria and pertussis, is given in five doses. 

These are administered in childhood when babies and children are seeing a pediatrician frequently, so it’s easier to ensure the immunizations are given in the correct time frame. In fact, the timing of young children’s checkups is built around immunization schedules to make it as easy as possible for parents.

Get daily coronavirus updates in your inbox: Sign up for our newsletter now.

In adults, things are more complicated. Hepatitis B, HPV, Hepatitis A and shingles vaccines all require a series of two to three doses for adults, and most adults who need them haven’t gotten them, in part, because completing the series can be hard, said Moore, of the Immunization Action Coalition.

Undertaking a two-dose vaccine protocol for the entire country would require coordination and meticulous record-keeping. A key player will be state immunization registries, which are run by state health departments.

Mostly used now used to ensure children get all the vaccinations they need, the registries are gearing up to record and track the vaccinations of large numbers of adults, Moore said. 

The directors of the immunization programs in the state health agencies have set up work groups and are having calls every two weeks with CDC and then immunization registry managers, said Claire Hannan, executive director of the Association of Immunization Managers.

“We’re lucky to have time to prepare,” she said