The trial showed VLA2001 was ‘well tolerated with no safety concerns identified’, with neutralizing antibody titres at or above levels generally seen in convalescent sera.
In the study of 153 adults aged 18-55, three doses (low, medium and high) were tested with two doses administered three weeks apart.
The French vaccine company will now take the high dose regimen into a Phase 3 clinical trial, due to start by the end of this month. This could see Valneva apply for authorization in the UK in the fall this year.
The delivery of 60 million doses to the UK is now scheduled for the first quarter of 2022 (pushed back from an initial delivery data of H2 2021).
Other trials, including booster trials, involving antigen sparing doses, will also be evaluated.
VLA2001 uses Valneva’s Vero-cell platform, which is used for the company’s licensed Japanese encephalitis vaccine, IXIARO. It consists of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018 (from Dynavax Technologies).
Valneva champions a ‘tried and tested’ approach with its inactivated candidate: drawing on established technology that has been in use for decades. It also says inactivated vaccines could prove to help people with weakened immune systems who are at greatest risk (population groups new vaccines do not yet have much data on) – such as pregnant women and certain immunocompromised patients.
And another advantage of the vaccine is that it would require only standard cold chain channels for distribution and storage (2 to 8°C).
Manufacturing capabilities are being scaled up at the company’s Livingston facility in Scotland following a vaccine partnership with the UK Government.
Thomas Lingelbach, Chief Executive Officer of Valneva, said: “We are extremely pleased with these [Phase 1/2] results which take us a step closer to providing an inactivated vaccine to help the global fight against COVID-19.
"The world needs multiple vaccines as well as booster options. Given the potential advantages often associated with inactivated whole virus vaccines, we believe that VLA2001 has an important role to play.
"This includes potential modifications to the vaccine to address variants, using our existing manufacturing process."
Phase 1/2 trial data
VLA2001 was 'generally safe and well tolerated across all dose groups tested', with no safety concerns identified by the independent Data Safety Monitoring Board.
No statistically significant differences were seen between dose groups and no differences between first and second vaccinations in terms of reactogenicity.
VLA2001 was 'highly immunogenic with more than 90% of all study participants developing significant levels of antibodies to the SARS-CoV-2 virus spike protein across all dose groups tested'.
Seroconversion Rates (SCR) for S-protein binding IgG antibodies were 89.8% in the medium dose and 100% in the high dose group. Two weeks after completion of the two dose schedule, Geometric Mean Fold Rise (GMFR) from baseline were 26 in the medium dose and 86 in the high dose group.
The IgG antibody response was highly correlated with neutralization titres in a micro-neutralization assay (MNA50) (r=0.79, p<0.001).
The vaccine induced a dose dependent response with statistically significant higher Geometric Mean Titres (GMTs) for both IgG and neutralizing antibodies in the high dose group compared to the low and medium dose groups. In the high dose group, the GMT of neutralizing antibody titres measured two weeks after completion of the two-dose schedule was at or above levels for a panel of convalescent sera (GMT 530.4 (95% CI: 421.49, 667.52)).
With a GMT ratio of vaccine vs. convalescent sera ≥ 1 vaccine efficacy has been reported above 80% for other vaccines.
VLA2001 induced broad T-cell responses across participants with antigen-specific IFN-gamma producing T-cells against the S-protein, M and N protein detected in 75.6 %, 35.6% and 48.9% of study participants, respectively.