Safety and immunogenicity of SARS-CoV-2 self-amplifying RNA vaccine expressing an anchored RBD: A randomized, observer-blind phase 1 study

Akahata, Wataru; Sekida, Takashi; Ode, Hirotaka; Tamura, Tomokazu; Kono, Kaoru; Kazami, Yoko; Washizaki, Ayaka; Masuta, Yuji; Suzuki, Rigel; Matsuda, Kenta; Komori, Mai; Morey, Amber L.; Ishimoto, Keiko; Nakata, Misako; Hasunuma, Tomoko; Fukuhara, Takasuke; IWATANI, Yasumasa; Yamamoto, Takuya; Smith, Jonathan; Sato, Nobuaki

doi:10.1016/j.xcrm.2023.101134

Cited by 12 publications

(12 citation statements)

References 32 publications

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“…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.…”

Section: Discussionmentioning

confidence: 71%

“…11 Both vaccines were well tolerated and demonstrated a lower incidence of solicited local and systemic AEs in the elderly compared with the non-elderly cohort, and no unsolicited AEs of concern. 11 Importantly, the modified vaccine, VLPCOV-02, demonstrated a more favorable safety profile compared with VLPCOV-01, although there has been no direct, head-to-head comparison between the two vaccines. Most solicited AEs for both the VLPCOV-01 and VLPCOV-02 vaccines were rated as mild or moderate.…”

Section: Discussionmentioning

confidence: 86%

“…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…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Aboshi,

Matsuda,

Kawakami

et al. 2023

Preprint

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Continuing emergence of variants of concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure of VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 vaccine with a comparable immune response to BNT162b2, was revised by incorporating a modified base, 5-methylcytosine to reduce reactogenicity, and an updated receptor-binding domain derived from Brazil (gamma) variant. Interim analyses of a phase 1 dose-escalation booster vaccination study with the resulting construct, VLPCOV-02, in healthy, previously vaccinated Japanese individuals (N=96) are reported (jRCT2051230005). A dose-related increase in solicited local and systemic adverse events was observed, which were generally rated mild or moderate. The most commonly occurring events were tenderness, pain, fatigue, and myalgia. Serum SARS-CoV-2 immunoglobulin titers increased during the 4 weeks post-immunization. VLPCOV-02 demonstrated a favorable safety profile compared with VLPCOV-01, with a lower frequency of adverse events and fewer fever events at an equivalent dose. These findings support further study of VLPCOV-02.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%