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ZURICH (Reuters) – Vaccines from AstraZeneca, Russia’s Gamaleya Institute and Johnson & Johnson fight the coronavirus with another virus, leaving scientists concerned that the vaccines could lose potency if annual vaccines become necessary to combat the new variants. So-called viral vector injections, also used by several Chinese COVID-19 vaccine developers, 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 against the vector itself, recognizing that it is an intruder and trying to destroy it.
Most vector vaccine developers have chosen to use an adenovirus, a harmless class of common cold virus. “The experience with adenoviruses has been for many years 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 of the University of Mainz.
“There may be the same problem with other types of vectors. Only ‘trial and error’ will tell,” he added.
That potentially puts vector vaccines at a disadvantage relative to injections of mRNA from Pfizer and Moderna, or vaccines that use inactivated coronaviruses, such as Sinovac, or coronavirus surface spike proteins, an approach pursued by Novavax. Vector immunity is not a new problem, but it has come under new scrutiny as companies like J&J anticipate that regular COVID-19 vaccines, such as annual flu shots, may be needed to combat new variants of the coronavirus. .
Moderna, as well as Pfizer and its partner BioNTech, said in separate statements this week that they are studying additional booster injections that point to new variants over time.
Even without any evolution of the virus, it is still unclear whether vaccine-induced immune memory will eventually decline, which would also require booster shots. Scientists who spoke to Reuters acknowledged that no definitive conclusions can be drawn about the ultimate impact of vector immunity.
While it may be surmountable in the end, health policy makers will still have to grapple with the question of which vaccines to implement, and in what order, before possible repeat inoculations.
An important validation of the vector 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 vector immunity has been implicated in past failures, including when a 2004 trial of Merck’s AIDS vaccine 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), which is responsible for marketing the Sputnik vaccine made by the Gamaleya Institute abroad, did not respond to a request for comment.
MIX AND COMBINE
One approach might be to combine different shots, known as “mix and match.”
The injection by AstraZeneca and its Oxford University partner is being tested with Russia’s Sputnik V, and British scientists are testing Pfizer’s mRNA injection with AstraZeneca’s vaccine in a British government-funded study, which says be aware of the problem of vector immunity.
The main reason for the British combined trial was to give healthcare providers flexibility in the event of limited supplies, but Matthew Snape, the Oxford vaccinologist leading the project, said the issue of vector immunity “is one of the reasons why which this study is interesting. ” He added that there were plans to test any vector reactions by seeing how well a viral vector works compared to an alternative vaccine when given as a third dose.
Plachter of the University of Mainz is among those who suggest that it may be more practical in the long term to switch to a vaccine class that does not depend on vectors. “If after a while, you come up with a standard immunization protocol, like with influenza, I would assume that you would use other carriers,” he said. AstraZeneca and the Gamaleya Institute have already tried to overcome the challenges of vector immunity with the standard regimen of two COVID-19 injections. The Russian lab used two different viral vectors, seeking to prevent efficacy from falling from the primary dose to the booster injection, while AstraZeneca and Oxford use a chimpanzee virus vector that humans would not have previously been exposed to. But the questions about a third shot or a subsequent shot have yet to be addressed.
“One of the big sales of (AstraZeneca) was that there can be no existing immunity,” said Ian Jones, professor of virology at the University of Reading. “This will not be the case once the world has received the COVID vaccines.”
Since the vectors in the major vaccines have lost their ability to replicate, the antibody and T cell responses they generate may, however, not be as strong. Also, 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 must be closely monitored because large amounts are injected. greater. “The injected dose is so low that the induction of immunity to the capsid, or coat of the virus, is still low,” said Luk Vandenberghe, a gene therapy expert at Harvard Medical School working on a COVID-19 vaccine. of viral vector.
(Information on 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)
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