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- Title
Development of a next-generation chikungunya virus vaccine based on the HydroVax platform.
- Authors
Slifka, Dawn K.; Raué, Hans-Peter; Weber, Whitney C.; Andoh, Takeshi F.; Kreklywich, Craig N.; DeFilippis, Victor R.; Streblow, Daniel N.; Slifka, Mark K.; Amanna, Ian J.
- Abstract
Chikungunya virus (CHIKV) is an emerging/re-emerging mosquito-borne pathogen responsible for explosive epidemics of febrile illness characterized by debilitating polyarthralgia and the risk of lethal infection among the most severe cases. Despite the public health risk posed by CHIKV, no vaccine is currently available. Using a site-directed hydrogen peroxide-based inactivation approach, we developed a new CHIKV vaccine, HydroVax-CHIKV. This vaccine technology was compared to other common virus inactivation approaches including β-propiolactone (BPL), formaldehyde, heat, and ultraviolet (UV) irradiation. Heat, UV, and BPL were efficient at inactivating CHIKV-181/25 but caused substantial damage to neutralizing epitopes and failed to induce high-titer neutralizing antibodies in vaccinated mice. HydroVax-CHIKV and formaldehyde-inactivated CHIKV retained intact neutralizing epitopes similar to live virus controls but the HydroVax-CHIKV approach demonstrated a more rapid rate of virus inactivation. HydroVax-CHIKV vaccination induced high neutralizing responses to homologous and heterologous CHIKV clades as well as to other alphaviruses including Mayaro virus, O'nyong'nyong virus, and Una virus. Following heterologous infection with CHIKV-SL15649, HydroVax-CHIKV-immunized mice were protected against viremia, CHIKV-associated arthritic disease, and lethal CHIKV infection by an antibody-dependent mechanism. In contrast, animals vaccinated with Heat- or UV-inactivated virus showed no protection against viremia in addition to demonstrating significantly exacerbated CD4+ T cell-mediated footpad swelling after CHIKV infection. Together, these results demonstrate the risks associated with using suboptimal inactivation methods that fail to elicit protective neutralizing antibody responses and show that HydroVax-CHIKV represents a promising new vaccine candidate for prevention of CHIKV-associated disease. Author summary: Chikungunya virus (CHIKV) is a mosquito-borne virus that has gained significant attention due to its ability to cause large epidemics and to spread beyond endemic countries through international travelers. Despite substantial efforts over the course of many years, a licensed CHIKV vaccine remains unavailable for protecting at-risk populations. Our research group has established an advanced site-directed oxidation system, termed HydroVax, for the development of new vaccines. Here, we describe a novel CHIKV vaccine that utilizes this peroxide-based vaccine platform and demonstrates greatly improved antiviral immunity compared to other traditional virus inactivation approaches as well as complete protection against viremia, CHIKV-associated arthritic disease and lethal CHIKV infection in robust preclinical mouse models. The HydroVax-CHIKV vaccine not only induced neutralizing antibodies to geographically diverse strains of CHIKV, but also elicited neutralizing antibody responses to other clinically important alphaviruses including, Mayaro, O'nyong'nyong, and Una virus. Together, this indicates that this vaccine not only protects against CHIKV infection but may potentially provide immunity across a broader range of virulent alphaviruses as well.
- Subjects
CHIKUNGUNYA virus; VIRAL vaccines; CHIKUNGUNYA; VIRUS inactivation; ANTIBODY formation; VACCINE development; PREVENTIVE medicine
- Publication
PLoS Pathogens, 2022, Vol 18, Issue 7, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1010695