LPP-based mRNA vaccine achieves up to 99% antibody formation against Delta and Omicron variants in Phase 1/2 clinical trial
Background
During the coronavirus disease-19 (COVID-19) pandemic, messenger RNA (mRNA) vaccines have played a pivotal role due to their rapid development and ability to induce strong immune responses. However, currently commercialized mRNA vaccines typically use lipid nanoparticles (LNPs) as delivery vehicles, which require ultra-cold distribution systems, making storage and transportation conditions extremely stringent. In particular, in countries with inadequate power supply or cold storage infrastructure, this poses a major obstacle to widespread vaccine distribution.
Limitations of the delivery system itself also remain a challenge. LNPs have been reported to accumulate excessively in specific organs or distribute systemically, potentially causing unexpected inflammatory responses. As a result, alternative technologies that improve biodistribution and ensure structural stability of vaccines are being actively explored.
In this context, Lipo-Polyplex (LPP) technology is emerging as a promising alternative to overcome the limitations of existing LNPs. LPP forms a core by combining mRNA with a polymer and is then enveloped by lipids, adopting a dual structure that significantly enhances thermodynamic stability. The clinical trial conducted in Laos was designed to demonstrate the actual safety and efficacy of this next-generation platform, which can function even in high-temperature and humid environments.
Key Findings
The research team evaluated the safety and immunogenicity of SW-BIC-213, an LPP-based candidate mRNA vaccine for COVID-19, in healthy adults in a phased manner. In Phase 1, 41 adults aged between 18 and 60 years were enrolled in an open-label, single-arm dose-escalation study, receiving 25 micrograms (μg) or 45 μg of the vaccine. All observed adverse reactions were mild, grade 1 or 2, supporting the vaccine's safety. Based on the results of Phase 1, the research team expanded the participant range and initiated Phase 2.
Participants were randomly assigned in a 2:2:1 ratio to the 25 μg dose group, 45 μg dose group, or placebo control group, and received a total of two doses 21 days apart. In the Phase 2 analysis, adverse reactions of grade 3 or higher were limited to transient fever. In terms of efficacy, notable immune responses were observed.
At 14 days after the second vaccination, pseudovirus neutralizing-antibody seroconversion exceeded 99% against the wild-type virus, 98% or higher against the Delta variant, 84% against the Omicron BA.1 variant, and 88% or higher against the BA.2 variant, confirming the vaccine's potential to defend against various variants. Neutralizing-antibody titers in both vaccinated groups were significantly higher than in the placebo group, clearly validating the efficiency of immune response acquisition.
Significance and Outlook
This study is of great significance in demonstrating the validity of LPP technology, developed as an alternative to existing LNP carriers, in actual human clinical trials. It provides a new technological breakthrough in the mRNA platform field, which has long struggled with biodistribution control and thermal stability issues. In particular, the fact that this next-generation vaccine delivery system can maintain efficacy in high-temperature and humid environments, such as those in developing countries, offers an opportunity to improve global health equity.
The consistently high seroconversion rates against various variant viruses are also encouraging. This suggests that the LPP platform not only enhances delivery efficiency but also effectively stimulates the immune system to form antibodies. It is expected that this platform can be extended to the development of vaccines for other infectious diseases such as influenza or respiratory syncytial virus (RSV) in the future.
However, long-term safety profile monitoring and validation of real-world preventive efficacy in large population groups remain challenges to be addressed. Follow-up research is needed to determine the duration of immune responses after vaccination and to confirm the long-term physicochemical stability under ambient storage conditions to achieve full commercialization.
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.
LPP-based vaccine technology offers a practical solution for strengthening disease prevention systems in developing countries and tropical climate regions with weak healthcare infrastructure. Existing LNP vaccines require ultra-cold cold chains as low as -70°C, making distribution nearly impossible in countries with unstable power supply and limited cold storage facilities. In contrast, the structurally stable LPP carrier maintains stability under standard refrigeration at 2–8°C or even under ambient temperature exposure, enabling safe transportation and supply to health centers in urban outskirts and remote island or mountainous areas in countries like Laos. This represents a decisive scenario for narrowing the global vaccine distribution imbalance and immunity gap. Furthermore, this platform technology can be immediately applied to the production of mRNA vaccines for infectious diseases prevalent in tropical regions, such as influenza or dengue fever, offering the added benefit of optimizing logistics costs in the biopharmaceutical industry.