In a head-to-head Phase III trial, Valneva’s inactivated, adjuvanted COVID-19 vaccine performed well against AstraZeneca’s non-replicating viral vector vaccine triggering higher levels of neutralizing antibodies, with similar numbers of mild-moderate infections seen in both groups.
Valneva is a French vaccine-focused biotech formed when the Austrian company Intercell and French company Vivalis merged in 2013. It has vaccines for chikungunya, Lyme disease and Zika virus under development and along with many other companies in this space joined the COVID-19 vaccine race after the start of the pandemic in 2020.
While it was not in the group of front runners to get vaccines to market like BioNTech/Pfizer, Moderna, J&J and AstraZeneca, it is now hoping to get its vaccine approved for future use. In what seems a sensible strategy, given several vaccines are already approved, it has taken a comparative approach to testing its vaccine candidate.
The French company is using a much more traditional vaccine technology than the currently approved COVID-19 vaccines—an inactivated version of the virus combined with an ‘adjuvant’ booster to trigger the most effective immune reaction to the shot. Many vaccines already use similar technology including standard flu vaccines.
Similar to most of the other COVID-19 vaccines, it requires 2 shots, although it has the benefit it can be stored between 2° and 8°C (35° to 46°F).
In a Phase III trial including 4012 participants in the UK, 1977 people received Valneva’s candidate and 995 received the AstraZeneca vaccine ChAdOx1-S as two intra-muscular injections given 4 weeks apart. Measurements of immunity were taken 2 weeks after the second dose at day 43.
Originally supposed to be a comparison in over 18’s, the company had to restrict its comparison to over 30’s after the UK government limited the use of the AstraZeneca vaccine to that age group due to blood clot fears. However, the Valneva vaccine was also tested in over 1000 individuals in the 18-30 age group.
The two primary endpoints of the study were for the Valneva candidate to produce a higher level of neutralizing antibodies than the AstraZeneca vaccine and also to have a similar or better seroconversion rate.
It met both these goals. The Valneva vaccine produced 39% more neutralizing antibodies than the AstraZeneca vaccine. The seroconversion rate was similar in both groups at 95% or above 2 weeks after participants had their final shot.
T-cell responses were analyzed in a subsection of participants. Broad antigen-specific IFN-gamma producing T-cells showing reactivity against the S, N and M proteins of the virus were seen in 74%, 46% and 20% of those tested, respectively.
Notably, the Valneva vaccine seemed to be well tolerated and induced less side effects than the AstraZeneca vaccine. For example, 91% of those in the AstraZeneca group had some kind of injection site reaction versus 73% of the Valneva group. Systemic reactions, such as feeling tired or unwell after vaccination, were also more common in the AstraZeneca than the Valneva group at 91% versus 70%.
The company did not quote numbers, but said in a press release that the number of mild-moderate COVID-19 cases was similar between the two cohorts and that no severe cases needing hospitalization were seen in either group.
“The low levels of reactogenicity and high functional antibody responses alongside broad T-cell responses seen with this adjuvanted inactivated whole virus vaccine are both impressive and extremely encouraging,” said the chief trial investigator Adam Finn, Professor of Paediatrics, University of Bristol, in the statement.
Valneva is planning to submit the vaccine for approval in the UK next month and is hoping approval might come before the end of the year. It also hopes the vaccine will be approved by the EMA in spring 2022. The company is continuing to run tests of the vaccine including trialing the vaccine for children and adolescents.
Like many of the COVID-19 vaccine developers with products still in development Valneva is hoping its vaccine could be used as a booster for people already vaccinated with other vaccines against the virus and joined a trial earlier in the year testing different COVID-19 vaccine boosters.
This positive result is a comeback for the French company. It is listed on the Euronext Paris and the news brought a rise in value of more than 30% for its shares, a pleasant contrast to the more than 40% drop they experienced last month when the UK government announced it had cancelled its order for 140 million doses of the vaccine.