A booster regime of liposome-delivered live-attenuated CHIKV vaccine RNA genome protects against chikungunya virus disease in mice

Shambhavi Rao; Eranga Abeyratne; Joseph R Freitas; Chenying Yang; Kothila Tharmarajah; Helen Mostafavi; Xiang Liu; Mehfuz Zaman; Suresh Mahalingam; Ali Zaid; Adam Taylor

doi:10.1016/j.vaccine.2023.05.032

A booster regime of liposome-delivered live-attenuated CHIKV vaccine RNA genome protects against chikungunya virus disease in mice

Vaccine. 2023 Jun 19;41(27):3976-3988. doi: 10.1016/j.vaccine.2023.05.032. Epub 2023 May 23.

Authors

Affiliations

¹ The Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, Southport, QLD 4215, Australia; School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Southport, 4215 Queensland, Australia; Global Virus Network (GVN) Centre for Excellence in Arboviruses, Australia.
² Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, 4222 Queensland, Australia.
³ The Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, Southport, QLD 4215, Australia; School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, Southport, 4215 Queensland, Australia; Global Virus Network (GVN) Centre for Excellence in Arboviruses, Australia. Electronic address: a.taylor1@griffith.edu.au.

PMID: 37230889
DOI: 10.1016/j.vaccine.2023.05.032

Abstract

Mosquito-transmitted chikungunya virus (CHIKV) is the causal pathogen of CHIKV disease and is responsible for global epidemics of arthritic disease. CHIKV infection can lead to severe chronic and debilitating arthralgia, significantly impacting patient mobility and quality of life. Our previous studies have shown a live-attenuated CHIKV vaccine candidate, CHIKV-NoLS, to be effective in protecting against CHIKV disease in mice vaccinated with one dose. Further studies have demonstrated the value of a liposome RNA delivery system to deliver the RNA genome of CHIKV-NoLS directly in vivo, promoting de novo production of live-attenuated vaccine particles in vaccinated hosts. This system, designed to bypass live-attenuated vaccine production bottlenecks, uses CAF01 liposomes. However, one dose of CHIKV-NoLS CAF01 failed to provide systemic protection against CHIKV challenge in mice, with low levels of CHIKV-specific antibodies. Here we describe CHIKV-NoLS CAF01 booster vaccination regimes designed to increase vaccine efficacy. C57BL/6 mice were vaccinated with three doses of CHIKV-NoLS CAF01 either intramuscularly or subcutaneously. CHIKV-NoLS CAF01 vaccinated mice developed a systemic immune response against CHIKV that shared similarity to vaccination with CHIKV-NoLS, including high levels of CHIKV-specific neutralising antibodies in subcutaneously inoculated mice. CHIKV-NoLS CAF01 vaccinated mice were protected against disease signs and musculoskeletal inflammation when challenged with CHIKV. Mice given one dose of live-attenuated CHIKV-NoLS developed a long lasting protective immune response for up to 71 days. A clinically relevant CHIKV-NoLS CAF01 booster regime can overcome the challenges faced by our previous one dose strategy and provide systemic protection against CHIKV disease.

Keywords: Alphavirus; Chikungunya virus; Liposome; RNA virus; Vaccine development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
Chikungunya Fever*
Chikungunya virus*
Liposomes
Mice
Mice, Inbred C57BL
Quality of Life
Vaccines, Attenuated
Viral Vaccines*

Substances

Liposomes
Vaccines, Attenuated
Viral Vaccines
Antibodies, Viral