People “combine and match” Covid vaccines over variant issues
Dr. Angela Rasmussen, a virologist at Georgetown University, received a booster dose of Covid-19 vaccine from Pfizer and BioNTech in late June, two months after receiving the single dose from Johnson & Johnson.
Rasmussen chose J&J in April when she was still living in Seattle because she wanted to move to Canada soon. She was concerned that she would not get the Pfizer vaccine, which requires two doses, because of the supply shortages in Canada at the time. J & J’s vaccine only requires one dose and recipients are considered fully vaccinated two weeks after receiving the vaccination.
But Rasmussen quickly changed her mind about Pfizer’s vaccine when it arrived in Canada. Delta, the highly transmissible variant first found in India and now represented in at least 124 countries, made headlines, and studies at the time indicated that a single dose of a Covid vaccine would not be enough.
“When the supply issues were being addressed here in Canada and there were really no shortages of mRNA vaccines, I decided to get a Pfizer injection just because I thought it wouldn’t do any harm in the worst case,” CNBC said in one Telephone interview.
Some Americans say they are finding ways to get extra doses of the Covid vaccines, some even go so far as to get the extra vaccinations from different companies. The thought is that by “mixing and matching” vaccines using different platforms, people may get broader protection from the coronavirus and its new variants. J & J’s vaccine uses an adenovirus, while Pfizer and Moderna’s two-dose vaccines use mRNA technology. It underscores the growing fear many Americans have about variants, including Delta, already the dominant form of the disease in the US
In other parts of the world the practice is nothing new. Last month, the German government said Chancellor Angela Merkel received the shot from Moderna in June after receiving the one from AstraZeneca in April. Other countries, such as Italy, also allow people under the age of 60 who received a first dose of AstraZeneca vaccine to have a different vaccination at the second dose. South Korea said last month that it would allow around 760,000 people to receive various jabs there due to delivery delays.
Pfizer, Moderna and J&J executives have said they expect Americans to need booster shots, and Pfizer has announced it will ask the FDA to authorize booster shots as it sees signs of waning immunity. The Centers for Disease Control and Prevention currently does not recommend mixing Covid vaccinations for Americans in most cases, and federal health officials say that otherwise healthy people do not currently require booster doses of the vaccines, although they may do so for the elderly or recommend to people with weakened immunity.
Since Rasmussen received her booster, a new study has found that the J&J vaccine against the Delta and Lambda variants is much less effective than against the original virus. The researchers who led the study, which has not yet been peer-reviewed, are now hoping that J&J recipients will eventually receive a booster of the Pfizer or Moderna vaccines.
The new research contradicts a study by the company that found the vaccine to be effective against Delta even eight months after vaccination, especially against serious illness and hospitalization. It is likely that the mixing and matching debate in the US will rekindle as the highly contagious Delta variant continues to spread in the US
“I would suspect that those who received a single dose from Johnson & Johnson may need a booster dose of an mRNA vaccine than other people need a booster dose,” said Dr. Isaac Bogoch, professor of infectious diseases at the University of Toronto, who was not involved in either study.
It is important for scientists and public health officials to be “open minded” about this, Bogoch said, adding that he is waiting for real data to back up the new study.
Israel also released preliminary data last week showing that the Pfizer vaccine there was only 39% effective against the virus, which officials attributed to the rapidly spreading Delta variant. Its effectiveness against serious illness and death remained high, the data showed. US and World Health officials said they would look at Israeli research, which was non-peer-reviewed and had few details.
The National Institutes of Health began an early-stage study in June looking at mixing and matching Covid vaccines. The study will enroll adults who have received any of the three Covid vaccination regimens currently available in the US: J&J, Moderna, or Pfizer. Scientists there are trying to find out whether there are advantages or disadvantages to using different boosters, according to the NIH.
A separate study from the UK published last month found that mixed doses of the AstraZeneca vaccine, which has technology similar to that of J&J, and an mRNA vaccine produced a stronger immune response against the coronavirus spike protein than just two doses AstraZeneca. The study, called Com-COV, compared mixed two-dose regimens of Pfizer and AstraZeneca vaccines.
Another study published Monday in Nature Medicine found that adding the Pfizer or Moderna vaccines as a second dose to J&J resulted in a better immune response than just two doses of the J&J vaccine and was well tolerated. The vaccinations were carried out between January 10th and April 8th.
Immunologically, it “makes sense” to follow a vaccination with another vaccination that uses a different platform, according to Yale immunologist Akiko Iwasaki.
“The reason for this is that if you use a vectorized vaccine like J&J or AstraZeneca that use adenovirus, you’re making antibodies to the vector, so your second vaccination with the same vector will reduce the chance of inducing a robust immune response,” she said.
Covid aside, there is nothing unusual about mixing and matching vaccines using different platforms, she said. If you look at vaccine studies and trials for HIV, “it’s almost standard for people to use different platforms to prepare and empower,” she said.
Mixing vaccines can prevent the body from causing some sort of “mediated clearance of the vaccine itself,” where the shot is less effective, Iwasaki said.
“The spike protein used for the J&J and Moderna and Pfizer vaccines is virtually identical so you won’t get cross-reactive protection against different variants,” she said. “But if you generate much higher levels of neutralizing antibodies, it will find epitopes in the variant that can also protect against the variant.”
Mixing the Covid vaccines seems safe, but at the same time, “we don’t know what we don’t know,” said Dr. Dan Barouch, an immunologist at Harvard Medical School who helped develop the J&J vaccine.
“There is limited data on the safety or effectiveness of the approach, but in theory I see no reason that raises major safety concerns,” said Barouch. “But there are theoretical benefits in terms of immune response and potential improvements in efficacy.”
The chief scientist of the World Health Organization, Dr. Soumya Swaminathan, recently advised individuals against mixing and combining Covid vaccines from different manufacturers, saying the practice is a “data-free zone” and immunogenicity and safety still need further assessment.
“It’s a bit of a dangerous trend here,” Swaminathan said during an online WHO briefing on July 13.
Still, some doctors are already suggesting that immunocompromised populations, such as cancer or organ transplant patients, could benefit from an extra dose of the same or a different Covid vaccine, Barouch said.
A CDC advisory group on Thursday considered whether fully vaccinated Americans with compromised immune systems need a booster dose of a Covid vaccine after data shows they are less likely to have antibodies to fight the disease and more likely to have what is known as a breakthrough infection.
“The most difficult ones to vaccinate are people with immunosuppression,” Barouch said, adding that early data shows that the vaccine mixing and matching approach can be safe and effective for these populations.
Rasmussen, the virologist at Georgetown University, said she had no safety concerns or side effects other than a sore arm after receiving a booster of the Pfizer vaccine.
Matthew, a retired photographer from Los Angeles, also said he didn’t experience any bad side effects after a booster shot. Much like Rasmussen, Matthew received a single dose of the Pfizer vaccine several weeks after a single dose of J&J.
He said he opted for a booster dose because he was concerned about his protection from variants. After talking to his doctor about mixing and matching vaccines, Matthew concluded that it was safe to get his second syringe from Pfizer.
“When I got Johnson & Johnson I was maybe a few days tired and had severe pain in my calves for almost 48 hours,” said Matthew, 70, who asked not to use his last name to protect his privacy. “I felt fine after the second dose.”
Dr. Paul Offit, who advises the FDA on Covid vaccines, said the CDC should “provide more direction” and provide guidelines on how vendors should think about mixing and matching vaccines. Though he said he didn’t expect the CDC to endorse the practice until more data is available and U.S. studies are complete.
“It would be helpful to have some guidelines from the CDC on how to think about it,” he said. “It would be even more important to come up with studies that are perfectly made to actually answer some of these questions.”
Likewise, Barouch said he didn’t expect any new recommendations until more data were available.
“There will be a lot of data soon and then there will be recommendations for data drives,” he said.