By John Miller and Ludwig Burger
ZURICH (Reuters) – Vaccinations by AstraZeneca, the Russian Gamaleya Institute and Johnson & Johnson are fighting the coronavirus with another virus, causing scientists to worry that the shots could lose power if annual vaccinations are needed to fight new variants.
So-called viral vector recordings – 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 body also develops immunity to the vector itself, recognizing it as an invader and trying to destroy it.
Most vector vaccine developers have chosen to use an adenovirus, a harmless class of cold viruses. “The experience with adenoviruses has been for years that vectors can be intercepted by the immune system after repeated injections,” said Bodo Plachter, deputy president. director of the Institute of Virology at Mainz University’s teaching hospital.
“There could be the same problem with other types of vectors. Only ‘trial and error’ can see it,” he added.
This potentially brings vector vaccines to the detriment of Pfizer and Moderna mRNA recordings, or vaccines that use inactivated coronaviruses, such as those of Sinovac, or the coronavirus’ surface peak proteins, an approach that Novavax has pursued.
Vector immunity is not a new problem, but has come under renewed scrutiny as companies, including J&J, expect regular COVID-19 vaccinations, such as annual flu shots, to be needed to fight new coronavirus variants.
Moderna as well as Pfizer and partner BioNTech said in separate statements this week that they are studying additional boost shots that target new variants over time.
Even without any evolution in the virus, it is not yet clear whether the immune memory induced by vaccines will eventually decline, which also requires shots.
Scientists who spoke to Reuters acknowledged that no definitive conclusions could be drawn about the ultimate impact of vector immunity.
While this may be manageable in the end, health policymakers will still have to wrestle with the question of which vaccines to deploy, and in what order, before possible repeated vaccinations.
A major validation of vector technology was the approval of Merck & Co’s Ervebo vaccine against Ebola in 2019 and its use – and that of similar experimental vaccines – during outbreaks in Africa in previous years.
But vector immunity has been implicated in failures in the past, including when a Merck AIDS vaccine trial in men was 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.
MENG EN PAS
One approach might be to combine different recordings, known as ‘mix and match’.
AstraZeneca and Oxford University partner are being tested with Russian Sputnik V, and British scientists are testing Pfizer’s mRNA shot with AstraZeneca’s vaccine in a study funded by the British government, which says it is aware of the problem with the immunity of the vector.
The main motive for the UK combination trial was to give healthcare providers flexibility in case of limited stock, but Matthew Snape, the Oxford vaccineist who led the project, said the demand for vector immunity is one of the reasons why this study is interesting.
He added that there were plans to test for any anti-vector response by seeing how well a viral vector performs against an alternative vaccine when given as a third dose.
Mainz’s Plachter is among those who suggest that in the longer term it may be more practical to turn to a vaccine class that does not rely on vectors.
“If you were to get a standard immunization protocol after a while, like with the flu, I would assume you would use other carriers,” he said. AstraZeneca and the Gamaleya Institute have already tried to overcome vector immunity challenges in the standard COVID-19 two-shot regime. The Russian laboratory used two different viral vectors to prevent the effectiveness of the primary dose from falling after the booster shot, while AstraZeneca and Oxford used a chimpanzee virus vector to which humans would not have been previously exposed.
But questions about a third or subsequent shot have yet to be addressed.
“One of the biggest selling points for (AstraZeneca) was that no existing immunity could exist,” said Ian Jones, a professor of virology at Reading University. “That will not be the case once the COVID vaccines are in the world.”
However, since the vectors in the leading vaccines have been deprived of their ability to replicate, the antibody and T cell responses they generate may not be as strong.
In addition, only small vector volumes are required 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 much larger amounts are injected.
“The injected dose is so low that the induction of immunity to the cap, or virus shell, remains low,” said Luk Vandenberghe, an expert in gene therapy at Harvard Medical School, on a viral vector COVID-19. -vaccine.
(Reporting by Ludwig Burger in Frankfurt, John Miller in Zurich, Kate Kelland and Alistair Smout in London and Michael Erman in New York; edited by Josephine Mason and Kirsten Donovan)