Lipo-Polyplex mRNA vaccine SW-BIC-213 elicits neutralizing antibody responses in a phase 1/2 trial in Laos
Background: Human evaluation of a new delivery platform
The Lipo-Polyplex (LPP)-based COVID-19 messenger RNA (mRNA) vaccine candidate SW-BIC-213 elicited neutralizing antibody responses in a phase 1/2 trial involving healthy adults in Laos. The trial assessed safety and immunogenicity; it did not measure efficacy in preventing infection or severe disease.
LPP is a delivery platform in which positively charged protamine sulfate condenses mRNA into a core that is then enclosed in a lipid shell. The researchers designed this structure to improve mRNA protection, distribution to lymphoid organs, and storage stability. However, this trial did not demonstrate improved biodistribution in humans or room-temperature stability.
SW-BIC-213 encodes the full-length spike protein of the original Wuhan virus, incorporating mutations that stabilize its prefusion structure, among other changes. The study examined whether a vaccine using this antigen would also induce antibody responses against Delta and Omicron BA.1 and BA.2.
Key findings: Variant-specific neutralizing antibody responses after vaccination
Phase 1 was an open-label dose-escalation trial in adults aged 18–60 years. Forty-one participants were assigned; 40 received the first dose and 39 completed both doses. In phase 2, 480 adults aged 18 years or older were randomly assigned in a 2:2:1 ratio to the 25-microgram (μg), 45-μg, or placebo group. The trial was double-blind and placebo-controlled. The report states that 479 participants received the first dose and 376 received the second. Doses were given 21 days apart.
Adverse events reported in phase 1 were grade 1 or 2. Most events in phase 2 were also grade 1 or 2; injection-site pain, fever, fatigue, and headache were observed. Fever was the reported grade 3 reaction and resolved after treatment. These results support tolerability within the study population and observation period, but the trial was not large enough to rule out rare harms.
The abstract reported pseudovirus neutralizing-antibody seroconversion rates 14 days after the second dose of more than 99% against wild type, more than 98% against Delta, more than 84% against Omicron BA.1, and more than 88% against BA.2. These are measures of antibody response, not infection-prevention rates. Neutralizing-antibody titers in both vaccine groups were higher than in the placebo group, although neutralizing responses against Omicron were lower than those against wild type and Delta.
At 90- and 180-day follow-up, seroconversion rates for wild-type and Delta neutralizing antibodies and spike-binding antibodies remained relatively high. However, because infections were not systematically assessed during follow-up, the later antibody responses cannot readily be attributed to vaccination alone.
Implications and outlook: Preventive efficacy and distribution conditions require separate evaluation
These results provide human data that may inform further development and dose selection for an LPP-based candidate. The researchers said they selected 25 μg for booster evaluation. However, the trial did not assess clinical preventive efficacy or establish an immunological benchmark for protection, so the antibody results cannot be translated into actual preventive efficacy.
All participants were Asian, and the study did not assess cellular immunity or BA.4/5 and subsequent variants. Participants with known prior infection were excluded, but the absence of systematic polymerase chain reaction (PCR) testing or anti-nucleocapsid antibody testing leaves the possible influence of asymptomatic or undetected infections unresolved. The number of participants who received the second dose was also lower than the number assigned, a factor to consider when interpreting the results.
Storage conditions also require careful distinction. Before use, the trial vaccine was stored at −25–−15°C; after thawing, it was kept at 2–8°C and used during the same vaccination session. These handling conditions do not establish stability for long-term refrigerated storage or room-temperature distribution. Any practical supply advantage must be assessed using separate stability and transport data. The study design and results are available in the provided full text of the Vaccines paper.
BACKGROUND/OBJECTIVES: Messenger RNA vaccines can induce strong immune responses, but delivery, biodistribution, and storage stability remain important considerations. We evaluated the safety and immunogenicity of SW-BIC-213, a Lipo-Polyplex (LPP)-based mRNA vaccine against SARS-CoV-2, in healthy adults in Laos. METHODS: We conducted a seamless phase 1/2 clinical trial in healthy adults. Phase 1 enrolled adults aged 18-60 years in an open-label, single-arm dose-escalation study; phase 2 enrolled adults aged ≥18 years in a randomized, double-blind, placebo-controlled study. Participants received two doses 21 days apart. The primary endpoints were safety in phase 1 and safety and immunogenicity in phase 2. RESULTS: In phase 1, 41 participants received 25 or 45 μg of SW-BIC-213. In phase 2, 480 participants were randomized in a 2:2:1 ratio to receive 25 μg, 45 μg, or placebo. All phase 1 adverse reactions were grade 1 or 2; grade 3 reactions in phase 2 were limited to transient fever. At 14 days after the second dose, pseudovirus neutralizing-antibody seroconversion exceeded 99% against wild-type virus, 98% against Delta, 84% against Omicron BA.1, and 88% against BA.2. Neutralizing-antibody titers were higher in both vaccine groups than in the placebo group. CONCLUSIONS: Two doses of SW-BIC-213 showed an acceptable safety profile and substantial humoral immunogenicity in healthy adults aged ≥18 years.
Vaccine developers can use these data to inform dose selection and subsequent clinical trial design for an LPP-based candidate. For example, a booster study in people previously vaccinated with an inactivated vaccine could evaluate the 25 μg dose selected by the researchers while separately assessing antibody responses, actual efficacy in preventing infection and severe disease, and safety. This phase 1/2 trial itself did not establish the effects of booster vaccination. Interpreting antibody persistence will require more precise identification of prior infections and infections during follow-up; responses to later variants also require further evaluation. Supply planning must account for frozen storage and handling after thawing. Refrigerated or room-temperature distribution, and any reduction in logistics costs, should be assessed once stability and transport validation data under those conditions are available.