- Vaccination with an experimental shot developed by China's CanSino Biologics led to immune responses in nearly all of 508 healthy volunteers enrolled in a mid-stage study, data published Monday in The Lancet show.
- More than half of the participants in the study had high pre-existing immunity to the cold virus CanSino uses to deliver its gene-based vaccine, however, which appeared to weaken its effects significantly. Widespread exposure to CanSino's chosen viral vector could limit the usefulness of the vaccine, a shortcoming researchers on the study acknowledged.
- CanSino is among the leading developers of a coronavirus vaccine, having started its first human tests at nearly the same time as Moderna in the U.S.. Results from the Phase 2 study, which were unblinded in mid-June, helped support the Chinese military's emergency approval last month for use of the vaccine in its soldiers.
CanSino's dataset, from a Phase 2 study of 508 healthy adults in Wuhan, China, is the second largest to be made public from the past five months of intense efforts to quickly advance vaccines against the new coronavirus.
The largest belongs to the University of Oxford, which along with AstraZeneca published initial results from a trial of 1,077 health volunteers on Monday, also in The Lancet.
Taken together, the data on the two candidates are encouraging, showing rapidly constructed vaccines can be safe while effectively spurring the body to produce antibodies against a key coronavirus protein. Researchers from both Oxford and CanSino also showed their shots were able to elicit a second kind of immune response, one that involves T cells rather than antibodies.
"The results of both studies augur well for Phase 3 trials," wrote Naor Bar-Zeev and William Moss of Johns Hopkins Bloomberg School of Public Health, in an accompanying editorial.
Neither CanSino's nor AstraZeneca's results can prove their respective vaccines protect against coronavirus infection or COVID-19, and limited follow-up means it's hard to assess how they might perform over time. Varied tests for measuring antibody and cellular responses make direct comparisons difficult, too.
But CanSino's data suggests several limitations which might make the company's vaccine less attractive.
Testing revealed all 508 study participants had some antibodies already present against the cold virus CanSino uses in its vaccine, suggesting those individuals were previously exposed and had built up defenses. The cold virus, adenovirus type 5, is needed to shuttle genetic instructions encoding the coronavirus' spike protein into the body's cells.
Pre-existing immunity to CanSino's choice of viral vector could mean those instructions don't make it into the target cells, potentially compromising the effects of vaccination. In the 266 study participants with high levels of adenovirus type 5 antibodies, that appeared to be the case.
Results showed antibodies to the coronavirus spike protein — what the vaccine is designed to elicit — were on average only half as high in people with high pre-existing immunity as those with low pre-existing immunity.
"Pre-existing anti-Ad5 immunity is considered to be the biggest obstacle for the candidate Ad5-vectored COVID-19 vaccine to overcome," the study authors wrote.
Usually, a vaccine could be given multiple times in order to boost antibody responses to levels scientists think are protective. But with viral vector vaccines like CanSino's that might be harder to do.
Oxford and AstraZeneca, by comparison, use an adenovirus commonly found in chimpanzees. In their results, only one of 98 tested participants had high pre-existing immunity to the viral vector.
CanSino's data showed other shortcomings. Measured by one type of test, only 59% and 47% of participants given the higher or lower dose of the vaccine developed so-called "neutralizing antibodies" capable of eliminating the SARS-CoV-2 virus. T cell responses were observed, but the levels appear well short of the mark set by Oxford and AstraZeneca. (They were measured at different time points in the studies, however.)
Nearly 15% of participants in CanSino's study were older than 55, a group that's particularly at-risk for developing symptomatic COVID-19. Previous trial results from other groups, including Oxford and AstraZeneca, were in younger adults aged 18 to 55.
The data in older trial volunteers showed some reason for caution, as average antibody levels were lower than in the below 55 years old group. For any vaccination campaign to be effective, older individuals will need to be protected as well as younger people.