Safety and Immunogenicity of SARS-CoV-2 Self-Amplifying RNA Vaccine Expressing Anchored RBD: A Randomised, Observer-Blind, Phase 1 Study

Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine, in healthy individuals

“…A similar phase 1 study (VLPCOV-01-0102) directly compared booster vaccination with VLPCOV-01 (dosed at 0.3, 1, or 3 µg) with the mRNA BNT162b2 vaccine (30 µg) or placebo (0.9% saline) in 92 healthy Japanese adults (aged 18 to ≥65 years) who had completed two doses of BNT162b2 6-12 months previously. 11 That study revealed a comparable safety profile between VLPCOV-01 and BNT162b2. No new safety signals were identified with VLPCOV-02 over those reported for VLPCOV-01.…”

“…Severe solicited systemic AEs were encountered predominantly among participants who received 15 µg VLPCOV-02, regardless of age; only one occurred at the lower doses of VLPCOV-02, 1-3 µg, compared with nine among participants receiving VLPCOV-01 at doses of 0.3-3 µg. 11 Of particular note, VLPCOV-02 appeared to be less reactogenic than VLPCOV-01, as suggested by comparison of rates of fever in participants receiving the same dose of vaccine. Among the 20 participants who received 3 µg VLPCOV-01, six (30.0%) experienced fever, of whom five were from the non-elderly cohort (n = 10, 50%) and one was from the elderly cohort (n = 10, 10%).…”

“…9,10 A novel COVID-19 vaccine, VLPCOV-01, was developed using the LNP-encapsulated saRNA platform derived from an alphavirus amplification system that encodes replicase and transcriptase functions comprising the alphavirus nonstructural proteins (nsp1-4) from the attenuated TC-83 strain of Venezuelan equine encephalitis virus (VEEV), and which expresses a membrane-anchored receptor-binding domain (RBD). 11,12 When delivered as a booster vaccine in the phase 1 VLPCOV-01-0102 clinical trial, VLPCOV-01 induced strong and persistent immune responses in both non-elderly and elderly healthy participants who had received primary vaccination with BNT162b2; neutralizing antibody titers to Wuhan, Delta, and Omicron variants of SARS-CoV-2 were observed. 11 The immune response achieved was comparable to that observed with BNT162b2 and with a similar safety profile, but at one-tenth of the vaccine dose.…”

“…11,12 When delivered as a booster vaccine in the phase 1 VLPCOV-01-0102 clinical trial, VLPCOV-01 induced strong and persistent immune responses in both non-elderly and elderly healthy participants who had received primary vaccination with BNT162b2; neutralizing antibody titers to Wuhan, Delta, and Omicron variants of SARS-CoV-2 were observed. 11 The immune response achieved was comparable to that observed with BNT162b2 and with a similar safety profile, but at one-tenth of the vaccine dose.…”

mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting

“…How the membrane-anchored RBD-TM compares with secreted RBD vaccines in terms of mechanism of action and potency is not known but is currently under investigation. We were not aware of any other parallel developments of membrane-anchored mRNA RBD vaccines until a recent report of a Phase 1 clinical study of a self-amplifying RNA construct was published ( 39 ). The advantage of mRNA RBD-based vaccines is the speed with which the product can be modified as the virus mutates, and the potential for design of multivalent vaccines.…”