A work in progress: Liposomes that induce soluble antigens to spontaneously convert to particles

Spontaneous nanoliposome antigen particleization (SNAP) is a potenial vaccine candidate to induced stonger immune response

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Two years ago, I published a paper in Nature Nanotechnology, entitled “A malaria vaccine adjuvant based on recombinant antigen binding to liposomes” [1]. Our team developed a liposome technology platform that works by spontaneous nanoliposome antigen particleization (SNAP). We showed the potential for the technology to induce antibodies with enhanced magnitude for blocking malaria transmission in preclinical studies. The concept is to insert cobalt-porphyrin-phospholipid (CoPoP) into liposomes, and upon mixing it with His-tagged antigens, this results in stably assembly of the antigens into the liposome bilayer. This results in the fast, stable and simple formation of transmission-blocking antigen particles, which we demonstrated enhance delivery to antigen-presenting cells and elicited long-term specific antibody generation in mice. It was humbling and thrilling to cooperate with experts in the malaria field from PATH-MVI and the NIH to carry out the highly multidisciplinary work.

Since the paper was published, the SNAP technology has continued to make inroads. In the past two years, we have extended our research of the SNAP platform to serve as a vaccine adjuvant not only in malaria transmission [2, 3], but also in other infectious diseases [4, 5]. In 2019, we received a Global Health Innovative Technology Fund to extend the malaria vaccine research. The project is in the collaboration with PATH-MVI, who has expertise in vaccine design, and Ehime University, who have experience in basic malaria research and can assess malaria infection in in vivo in mice. The goal of this study is to co-deliver two leading malaria vaccine antigen candidates using the SNAP system, in order to block parasite transmission from human-to-mosquito and mosquito-to-human. Our preliminary data shows that the co-delivery system can induce strong and balanced antibodies in mice and rabbits. The dual-antigen particles are stable for months of storage in the fridge

One of our most recent achievements was to develop an antigen-particle vaccine against SARS-CoV-2[6]. The receptor-binding domain of SARS-CoV-2 is a target for vaccine development and generating antibodies against this domain effectively neutralizes the virus. In this study we found that forming antigen-particles using the receptor-binding domain itself presented on SNAP liposomes could induce strong immune responses, and this could be a promising strategy for COVID-19 vaccine development. The potent immune response is due to converting the antigen into nanoparticles, which could mimic the nature of the virus itself, and could generate higher level of neutralizing antibodies. We hope that we can bring this approach into human clinical trials soon.

The work we published in Nature Nanotechnology has opened the door for many opportunities for us to extend our research on SNAP with collaborations, in both academic fields and with pharmaceutical companies. I have joined POP Biotechnologies, a University at Buffalo spinout company and it has been exciting working with several vaccine makers who are interested in the technology. We are eager to pursue these opportunities and are seeking for further collaborations to work on vaccines for other diseases using the platform.

Reference

[1] Huang W-C, Deng B, Lin C, Carter KA, Geng J, Razi A, He X, Chitgupi U, Federizon J, Sun B, et al: A malaria vaccine adjuvant based on recombinant antigen binding to liposomes. Nature Nanotechnology 2018, 13:1174-1181.

[2] Huang WC, Deng B, Mabrouk MT, Seffouh A, Ortega J, Long C, Miura K, Wu Y, Lovell JF: Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose. Malar J 2020, 19:309.

[3] Huang WC, Deng B, Seffouh A, Ortega J, Long CA, Suresh RV, He X, Miura K, Lee SM, Wu Y, Lovell JF: Antibody response of a particle-inducing, liposome vaccine adjuvant admixed with a Pfs230 fragment. NPJ Vaccines 2020, 5:23.

[4] Shao S, Huang WC, Lin C, Hicar MD, LaBranche CC, Montefiori DC, Lovell JF: An Engineered Biomimetic MPER Peptide Vaccine Induces Weakly HIV Neutralizing Antibodies in Mice. Ann Biomed Eng 2020, 48:1991-2001.

[5] Federizon J, Frye A, Huang WC, Hart TM, He X, Beltran C, Marcinkiewicz AL, Mainprize IL, Wills MKB, Lin YP, Lovell JF: Immunogenicity of the Lyme disease antigen OspA, particleized by cobalt porphyrin-phospholipid liposomes. Vaccine 2020, 38:942-950.

[6] Huang WC, Zhou S, He X, Chiem K, Mabrouk MT, Nissly RH, Bird IM, Strauss M, Sambhara S, Ortega J, et al: SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination. Adv Mater 2020:e2005637.

Wei-Chiao Huang

University at Buffalo/ Postdoctoral Fellow , Biomedical Engineering department

My present work is focused on the development and validation of liposomal vaccine adjuvants. I have worked in malaria transmission-blocking vaccines in collaboration with the PATH Malaria Vaccine Initiative (PATH-MVI) and the Global Health Innovation Technology Fund (GHIT). I have over seven years of working with liposomes, and over four years of experience in vaccine development, antigen-liposomes conjugation and mice immunization.

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