A previous coronavirus infection combined with one dose of Covid vaccine – is it effective?
A rising number of studies suggest that many individuals who have been infected with the coronavirus may be able to safely bypass the second dose of any two-dose vaccine regimen.
These findings have the potential to help stretch finite vaccine supplies, and they are already impacting vaccination strategies in several nations.
However, questions remain regarding whether the findings apply to all people and all vaccines – and hence how policymakers should respond to the findings.
According to studies, patients who have previously been exposed to SARS-CoV-2 have significant immune responses to single doses and get little benefit from second injection. Furthermore, for people who have acquired immunity through infection, one dosage often raises antibody levels to levels equivalent to, or often higher than, those reported in individuals who have not been infected and have received multiple doses.
France, Germany, and Italy, among others, now recommend only one shot of vaccine for individuals with a good immune system and a verified prior diagnosis. Many scientists who have researched immunological responses to vaccination believe that such rules are a rational method to make the most of limited supply in countries that are rushing to immunise their populace.
“To follow the current two-dose vaccination schedule in previously infected individuals, when there are millions of people waiting for their first dose, simply does not make sense,” says immunologist Jordi Ochando from the Icahn School of Medicine.
However, scientists are still unsure whether one-jab regimens for previously infected people will provide adequate protection to some people. It’s also unclear if such plans would be effective for all types of vaccines.
“If you have been infected before, then probably one dose is sufficient,” says immunologist Giuliana Magri from the Hospital del Mar Research Institute in Barcelona, Spain.
But what about putting that information into action? “It’s complicated,” she admits.
Just one shot
There is sufficient laboratory evidence that people infected with SARS-CoV-2 benefit from vaccination, prompting the WHO and other public agencies to recommend that such people be vaccinated. However, it is unclear whether they must roll up their sleeves twice.
Research published in Nature gives some of the most recent evidence that for people who have received COVID-19, one shot may be all that is required. A group of experts from Rockefeller University in New York City and abroad evaluated 26 patients who became infected with the virus early in the outbreak. They were all given at least one dose of either the Pfizer–BioNTech or the Moderna vaccines, which are both based on messenger RNA.
The researchers looked at participants’ levels of ‘neutralizing antibodies,’ which are powerful immune molecules that can prevent viruses from entering cells. Currently, the quantity and strength of a person’s neutralizing antibodies are the best indicators of whether that person is resistant to infection and sickness — however scientists are still striving to demonstrate that antibody levels may serve as a realistic stand-in for immune protection.
The researchers also looked at participants’ memory B cells, which recall infections and can quickly produce targeted antibodies if they come across an infectious agent they’ve encountered before. Within a month or two of vaccination, research participants’ levels of memory B cells had increased almost 10-fold on average, and their ‘titres,’ or levels of neutralizing antibodies, had increased nearly 50-fold. Those gains were evident in previously infected participants who had received one or two shots.
In fact, in people with no prior illnesses, a single dose of vaccine produced titres that were equal to – or higher than – those produced by two doses of vaccine.
“It’s really amazing,” says the co-author and virologist Theodora Hatziioannou.
“I wish everyone’s titres were like this.”
Memory booster
Hatziioannou and her colleagues’ findings also point at the biochemical basis of one jab’s effectiveness in exposed people. Memory B cells were not static in the 12 months after people were infected. Instead, those cells evolved for a complete year, allowing them to make antibodies that were much more strong and flexible than those produced immediately after infection.
Other research back up that theory, with some demonstrating that a single shot can stimulate the creation of antibodies as well as infection-fighting T cells.
“We’re all seeing pretty much the same thing,” says John Wherry, an immunologist at the University of Pennsylvania Perelman School of Medicine in Philadelphia. For people who have recovered from COVID-19, “the second shot doesn’t seem to do a whole lot”.
Although most research on the subject has focused on mRNA vaccines, preliminary evidence from studies conducted in the United Kingdom and India suggests that single-dose strategies may be successful if they rely on the Oxford-AstraZeneca shot, which uses an engineered adenovirus to stimulate an immune response against SARS-CoV-2.
Another research, for example, found that one dose of the AstraZeneca jab elicited a substantially stronger immune response in infected health-care workers than in uninfected peers.
The findings “support a single-dose vaccination strategy for previously infected individuals to increase coverage and protect a larger number of populations”, the authors write.
According to Stacy Wood of North Carolina State University in Raleigh, a marketing specialist who has examined vaccination messaging, a one-jab policy for people who have been infected may even help to overcome vaccine ambivalence. She contends that, rather than causing uncertainty, outreach that takes into account individual traits can help persuade people who believe their own circumstances, including infection history, make them special. Reducing the number of shots — and all the associated side effects, fear, and time — might also be an appealing prospect for those who are on the fence about becoming immunized.
“The more tailored approach is probably better at this point,” Wood says.
Stretching vaccine doses
The mounting evidence has persuaded many scientists that second doses of a valuable vaccine should not be given to those who have been affected.
Providing only one dose to those who’ve had COVID-19 “would free up many urgently needed vaccine doses. With the additional available vaccines, there would be no need to delay the second vaccine dose for naïve individuals,” argues a letter published in May in EBioMedicine and signed by eight COVID-19 scientists.
And, increasingly, governments and regions with vaccination shortages are following the scientists’ lead, at least for younger persons with healthy immune systems.
However, not all governments are on board with this strategy. In the United States, where vaccination is reasonably abundant, experts nonetheless suggest two doses for everyone.
Determining prior infection history “is not recommended for the purposes of vaccine decision-making”, says Kate Grusich, a spokesperson for the US Centers for Disease Control and Prevention in Atlanta, Georgia.
Researchers also note that certain persons who become infected with SARS-CoV-2 have a comparatively weak immune response. Such a reaction is more common in those who do not acquire COVID-19 symptoms.
“There’s a huge range of antibody generation and durability in those individuals,” notes Wherry.
“Making decisions based on previous PCR-confirmed infections might miss some people.”
This is when diagnostic antibody testing can come in handy.
Antibodies to the hepatitis B virus are already routinely screened in some settings to guide vaccination strategies against that infectious agent, and the same could be done with antibodies to the SARS-CoV-2 spike protein, a marker of both natural and vaccine-induced immunity, according to Viviana Simon, an infectious disease specialist at Mount Sinai and a signatory to the EBioMedicine letter.
“When in doubt, I’m all for a second dose,” she says.
“But I personally hope that we can move eventually to more personalized schedules and recommendations.”
Source: Nature Study at doi: https://doi.org/10.1038/d41586-021-01609-4