FINLAY-FR-1A vaccine boosts natural immunity in COVID-19 convalescents

A single dose of FINLAY-FR-1A, a recombinant d-RBD*-based COVID-19 vaccine, strengthens pre-existing natural immunity in patients who have recovered from asymptomatic, mild or moderate COVID-19, and has an excellent safety profile, a phase IIa/b study has shown.

“People [who have] recovered from COVID-19 might be re-infected, particularly those with low neutralizing antibody titres and facing new SARS-CoV-2 variants of concern (VoCs),” said the researchers. “[Therefore, we] aimed to study the response of memory B cells after a single dose of the vaccine in individuals with past SARS-CoV-2 infection.”

“[Our study showed that] immunization with a single dose of FINLAY-FR-1A vaccine triggered a rapid induction of high humoral immune response, suggesting protective immunity against SARS-CoV-2, and a decrease in severe re-infection by SARS-CoV-2 VoCs,” they continued.

The study comprised 450 participants. Phase IIa evaluated the safety of a single dose of FINLAY-FR-1A in 20 participants aged 60–78 years. In phase IIb, participants aged 19–78 years (n=430; mean age 46 years, 56 percent female) were randomized 4:1 to receive either a single dose of FINLAY-FR-1A or a vaccine excipient (placebo arm). [Lancet Respir Med 2022;10:785-795]

 

Safety, reactogenicity

In phase IIa, there were no serious adverse events (AEs) reported 28 days post-vaccination. In phase IIb, site pain was the most frequent vaccine-associated AE (29 percent) among FINLAY-FR-1A recipients. None of the vaccine-associated AEs were serious. The first 24 hours following vaccination saw higher rates of local and systemic reactions, but these were mostly mild and disappeared within the first 3 days.

“The low [AE rate] and absence of serious events confirmed the safety of the experimental vaccine,” said the researchers.

 

Immunogenicity

In phase IIa, all but one mounted a successful immune response. In phase IIb, the proportion of participants achieving this endpoint was substantially higher in the FINLAY-FR-1A vs the placebo arm (81 percent vs 5 percent; p<0.0001).

RBD antibodies increased significantly 28 days post-vaccination (median, 301.0 U/mL). This was >30 times higher than the pre-vaccination concentration (9.7 U/mL) and nearly 50 times higher than that seen with placebo (6.6 U/mL; p<0.0001 for both comparisons).

“This study confirms – now in convalescent participants – the immunogenicity of FINLAY-FR-1A,” said the researchers. The successful stimulation of B cells for about 5 months following discharge and the high neutralizing antibody concentrations demonstrate that “natural infection leads to the production of long-term memory B cells that respond quickly to a single dose of FINLAY-FR-1A … and that a single dose induces a strong secondary immune response”.

There was also an increase in live-virus neutralizing titres against the Alpha, Beta, and Delta VoCs with FINLAY-FR-1A, with geometric mean titres jumping from 15.4 prior to vaccination to 400.3 28 days after vaccination (p<0.0001).

 

The verdict: safe, effective, immunogenic

“We selected a convalescent serum panel representative of the various clinical manifestations of COVID-19 to evaluate vaccine-induced immune response vs disease-acquired immunity, taking into account that during convalescence­, specific IgG antibodies contribute to immunologic protection against SARS-CoV-2,” the researchers explained. “Our results were superior to those of the convalescent serum panel, supporting vaccination in COVID-19 convalescent individuals.”

“[Overall, our results show that] FINLAY-FR-1A is a safe, effective, and immunogenic vaccine,” said the researchers. The findings also augment the results of the phase I trial. [Lancet Reg Health Am 2021;doi.org/10.1016/j.lana.2021.100079]

Future trials should evaluate COVID-19 convalescents with a history of severe disease to ascertain the potential association between induced immune response and clinical severity of SARS-CoV-2 infection. The effect of FINLAY-FR-1A in younger cohorts and against the Omicron variant and future emerging VoCs should also be investigated, the researchers noted.

Produced by the Instituto Finlay de Vacunas Cuba, FINLAY-FR-1A has been approved in Cuba as a booster dose following the two first doses of FINLAY-FR-2. [covid19.trackvaccines.org/vaccines/119]