A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques

Awadalkareem Adam; Courtney Woolsey; Hannah Lu; Kenneth Plante; Shannon M Wallace; Leslie Rodriguez; Divya P Shinde; Yingjun Cui; Alexander W E Franz; Saravanan Thangamani; Jason E Comer; Scott C Weaver; Tian Wang

doi:10.1038/s41541-024-01047-z

A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques

NPJ Vaccines. 2024 Dec 19;9(1):251. doi: 10.1038/s41541-024-01047-z.

Authors

Awadalkareem Adam^{1

2}, Courtney Woolsey^{1

3}, Hannah Lu¹, Kenneth Plante^{1

4}, Shannon M Wallace⁵, Leslie Rodriguez¹, Divya P Shinde^{1

4}, Yingjun Cui⁶, Alexander W E Franz⁶, Saravanan Thangamani⁷, Jason E Comer^{1

3}, Scott C Weaver^{1

2

3

4}, Tian Wang^{8

9

10

11}

Affiliations

¹ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
² Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, 77555, USA.
³ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, 77555, USA.
⁴ World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, 77555, USA.
⁵ Experimental Pathology Laboratories, Inc, Sterling, VA, 20166, USA.
⁶ Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, 65211, USA.
⁷ Department of Microbiology and Immunology, SUNY Upstate Medical University, 505 Irving Avenue, Syracuse, NY, 13210, USA.
⁸ Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. ti1wang@utmb.edu.
⁹ Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, 77555, USA. ti1wang@utmb.edu.
¹⁰ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, 77555, USA. ti1wang@utmb.edu.
¹¹ Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA. ti1wang@utmb.edu.

Abstract

Eilat (EILV)/chikungunya virus (CHIKV), an insect-based chimeric alphavirus was previously reported to protect mice months after a single dose vaccination. The underlying mechanisms of host protection are not clearly defined. Here, we assessed the capacity of EILV/CHIKV to induce quick and durable protection in cynomolgus macaques. Both EILV/CHIKV and the live attenuated CHIKV 181/25 vaccine protected macaques from wild-type (WT) CHIKV infection 1 year after a single dose vaccination. Transcriptome and functional analyses reveal that EILV/CHIKV triggered T cell, memory B cell and antibody responses in a dose-dependent manner. EILV/CHIKV induced more robust, durable, and broader repertoire of CHIKV-specific T cell responses than CHIKV 181/25; whereas the latter group induced more durable memory B cells and comparable or higher CHIKV -specific neutralization and binding antibodies. EILV/CHIKV and an inactivated WT CHIKV protected macaques from WT CHIKV infection and CHIK fever (CHIKF) within 6 days post vaccination. Transcriptome analysis showed that the chimeric virus induced multiple innate immune pathways, including Toll-like receptor signaling, antigen presenting cell activation, and NK receptor signaling. EILV/CHIKV triggered quicker and more robust type I interferon and NK cell responses than the inactivated WT virus vaccine. Lastly, we developed a guinea pig sensitization model and demonstrated that the chimeric virus produced in insect cells, did not cause skin hypersensitivity reactions. Overall, EILV/CHIKV is safe, and confers rapid and long-lasting protection in cynomolgus macaques via preferential induction of robust innate immune signaling and superior T cell immunity.

Abstract

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