By John Miller and Ludwig Burger
ZURICH (Reuters) – Vaccines from AstraZeneca, the Russian Gamaleya Institute and Johnson & Johnson fight against the coronavirus with another virus, leaving scientists worried about the vaccines’ potency if annual inoculations are needed to combat new variants.
So-called viral vector vaccines – also used by several Chinese vaccine developers COVID-19 – use harmless modified viruses as vehicles, or vectors, to carry genetic information that helps the body build immunity against future infections.
However, there is a risk that the organism also develops immunity to the vector itself, recognizing it as an intruder and trying to destroy it.
Most developers of vector vaccines have chosen to use an adenovirus, a harmless class of the common cold virus. “Experience with adenoviruses has shown that vectors can be intercepted by the immune system after repeated injections,” said Bodo Plachter, deputy director of the Institute of Virology at the university hospital at Mainz University.
“There may be the same problem with other types of vectors. Only ‘trial and error’ will say,” he added.
This potentially puts vector vaccines at a disadvantage compared to Pfizer and Moderna mRNA injections, or vaccines using deactivated coronaviruses, such as Sinovac, or peak surface proteins from coronavirus, an approach pursued by Novavax.
Vector immunity is not a new problem, but it is under renewed scrutiny, as companies, including J&J, predict that regular COVID-19 vaccinations, such as annual flu vaccines, may be needed to combat new variants of the virus. coronavirus.
Moderna, as well as Pfizer and partner BioNTech, said in separate statements this week that they are studying additional booster doses that target new variants over time.
Even without any evolution in the virus, it is still unclear whether the vaccine-induced immune memory will eventually decrease, which would also require booster doses.
Scientists who spoke to Reuters acknowledged that no definitive conclusions can be drawn about the final impact of vector immunity.
Although it may be surmountable in the end, health policymakers will still have to deal with the question of which vaccines to implant and in what order, before potential repeated inoculations.
An important validation of the vector’s technology was the approval of Merck & Co’s Ervebo inoculation against Ebola in 2019 and its use – and similar experimental vaccines – during outbreaks in Africa in previous years.
But the vector’s immunity has been implicated in previous failures, including when a Merck AIDS vaccine trial in 2004 failed in men previously exposed to the adenovirus used for the vaccine.
AstraZeneca declined to comment. J&J and the Russian Direct Investment Fund (RDIF), responsible for marketing the Sputnik vaccine made by the Gamaleya Institute abroad, did not respond to a request for comment.
MIX AND MATCH
One approach could be to combine different shots, known as “mixing and matching”.
The injection of AstraZeneca and the partner University of Oxford is being tested with Sputnik V from Russia, and British scientists are testing Pfizer’s mRNA injection with the AstraZeneca vaccine in a study funded by the British government, which it claims to be aware of. of the vector immunity problem.
The main reason for the British combination test was to give healthcare professionals flexibility in the case of limited supplies, but Matthew Snape, the Oxford vaccinologist who led the project, said the vector’s immunity issue “is one of the reasons why this study is interesting “.
He added that there are plans to test any anti-vector reaction, checking the performance of a viral vector compared to an alternative vaccine when administered as a third dose.
The University of Mainz Plachter is among those who suggest that it may be more practical in the long run to switch to a vaccine class that does not depend on vectors.
“If after a while you get a standard immunization protocol, as with flu, I would assume that you would use other carriers,” he said. AstraZeneca and Instituto Gamaleya have already sought to overcome the challenges of vector immunity under the standard two-dose regime COVID-19. The Russian laboratory employed two different viral vectors, seeking to prevent the effectiveness from falling from the primary dose to the booster dose, while AstraZeneca and Oxford use a chimpanzee virus vector that humans would not have previously been exposed to.
But questions about a third or subsequent attempt have yet to be answered.
“One of the great advantages of (AstraZeneca) is that there may be no immunity,” said Ian Jones, professor of virology at Reading University. “This will not be the case, once the world has the COVID vaccines.”
Since the vectors in the main vaccines have been deprived of their ability to replicate, the antibody and T cell responses they generate may, however, not be as strong.
In addition, only small volumes of vector are needed for COVID-19 vaccines, in contrast to gene therapies where viral vectors serve as gene repair kits for diseased cells and vector immunity needs to be closely monitored because too much larger ones are injected.
“The injected dose is so low that induction of immunity to the capsid, or virus shell, remains low,” said Luk Vandenberghe, a gene therapy specialist at Harvard Medical School who works on a COVID-19 viral vector vaccine.
(Reporting by Ludwig Burger in Frankfurt, John Miller in Zurich, Kate Kelland and Alistair Smout in London and Michael Erman in New York; Editing by Josephine Mason and Kirsten Donovan)