Safety and immunogenicity of SW-BIC-213, a modified COVID-19 Lipo-Polyplex mRNA vaccine, in Laotian healthy adults aged 18 years and above: a Phase 1/2 trial

Abstract

ABSTRACTBackgroundThe mRNA vaccine against SARS-CoV-2 has demonstrated remarkable efficacy in protecting against coronavirus disease 2019 (COVID-19), including providing high protection against severe disease during the emergence of variant waves. In this study, we aimed to investigate the safety and immunogenicity of a 2-dose regimen of the LPP-based mRNA vaccine, SW-BIC-213, in Laos.MethodsFor this phase 1/2 clinical trial, we recruited healthy adults aged 18-60 years (phase 1) or ≥18 years (phase 2) from Mahosot Hospital (Vientiane) and Champhone District Hospital (Savannakhet). Participants with SARS-CoV-2 infection, previous COVID-19 vaccination, known allergies to any vaccine component, or pregnancy were excluded. In the phase 1 trial, 41 eligible participants were sequentially assigned to either the 25 μg dose group (25 μg) or the 45 μg dose group (45 μg) in accordance with their enrollment order, with 21 participants in 45 μg dose group and 20 participants in 25 μg dose group. In the phase 2 trial, 480 participants were randomly allocated (2:2:1 ratio) to either the 25 μg dose group, 45 μg dose group, or placebo group.The primary endpoints for the phase 1 trial were the incidence of local/systemic solicited adverse reactions/events (0-6 days after each vaccination dose), unsolicited adverse events (0-21 days and 0-28 days after the first and second dose of immunization, respectively), and serious adverse events from the first dose of vaccination to 28 days after completing the full course of immunization. In the phase 2 trial, the primary endpoints were the seroconversion rate and geometric mean titer (GMT) of SARS-CoV-2 S-protein specific IgG antibodies and neutralizing antibodies 14 days after the second dose in participants. As for neutralizing antibodies, we detected pseudo-virus neutralizing antibody against wild type (WT), Delta, BA.1 and BA.2. We also detected live viral neutralizing antibody against WT strain 14 days after the second dose. Furthermore, the safety endpoints were also measured during the trial.This seamless phase 1/2 trial was registered withClinicalTrials.govunder the identifierNCT05144139.ResultsBetween December 3, 2021, and March 31, 2022, a total of 41 participants were recruited in the phase 1 trial, while the phase 2 trial enrolled 480 participants from January 20 to July 6, 2022. In the phase 1 trial, a total of 32 subjects (80.0%) reported 103 cases of adverse reactions. All adverse reactions were limited to Grade 1-2. In the phase 2 trial, a total of 479 subjects, 372 subjects (77.7%) reported 929 cases of adverse reactions. All adverse reactions in severity of Grade 3 were manifested as fever (3.4%, 2.1% and 2.9% in 45 μg dose, 25 μg dose and placebo group respectively, only observed in adults), except which all other reactions were limited to Grade 1-2. All adverse reactions noted during the study were tolerable, predominantly transient, and resolved spontaneously. No serious adverse events (SAEs) related to vaccination were observed.In Phase 2 study, SW-BIC-213 could elicit a high level of seroconversion rate of pseudo-virus neutralizing antibody against WT (100.0% in 25 μg dose group, 99.3% in 45 μg dose group), Delta (99.2% in 25 μg dose group, 98.0% in 45 μg dose group), Omicron BA.1 (84.1% in 25 μg dose group, 84.7% in 45 μg dose group) and Omicron BA.2 (96.0% in 25 μg dose group, 88.8% in 45 μg dose group) at 14 days after the second dose. The pseudo-virus neutralizing antibody titer against WT, Delta, BA.1 and BA.2 was all significant higher (P<0.0001) in both 45 μg dose group (1175.02, 620.62, 72.39 and 172.80) and 25 μg dose group (885.80, 579.40, 47.24 and 101.96) compared with the placebo group (9.67, 10.66, 13.99 and 29.53) at 14 days after the second dose. As for live viral neutralizing antibodies against WT strain, the seroconversion rate could reach more than 94% at 14 days after second dose. The neutralizing antibody titer against WT strain was significantly higher (P<0.0001) in both 45 μg dose group (315.00) and 25 μg dose group (323.18) compared with the placebo group (8.51) at 14 days after second dose.ConclusionCOVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and is highly immunogenic in eligible subjects aged ≥18 years.