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Non-replicating adenovirus based Mayaro virus vaccine elicits protective immune responses and cross protects against other alphaviruses
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 15, Iss 4, p e0009308 (2021)
- Publication Year :
- 2021
- Publisher :
- Public Library of Science, 2021.
-
Abstract
- Mayaro virus (MAYV) is an alphavirus endemic to South and Central America associated with sporadic outbreaks in humans. MAYV infection causes severe joint and muscle pain that can persist for weeks to months. Currently, there are no approved vaccines or therapeutics to prevent MAYV infection or treat the debilitating musculoskeletal inflammatory disease. In the current study, a prophylactic MAYV vaccine expressing the complete viral structural polyprotein was developed based on a non-replicating human adenovirus V (AdV) platform. Vaccination with AdV-MAYV elicited potent neutralizing antibodies that protected WT mice against MAYV challenge by preventing viremia, reducing viral dissemination to tissues and mitigating viral disease. The vaccine also prevented viral-mediated demise in IFN⍺R1-/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFN⍺R1-/- mice, indicating that antiviral antibodies are protective. Immunization with AdV-MAYV also generated cross-neutralizing antibodies against two related arthritogenic alphaviruses–chikungunya and Una viruses. These cross-neutralizing antibodies were protective against lethal infection in IFN⍺R1-/- mice following challenge with these heterotypic alphaviruses. These results indicate AdV-MAYV elicits protective immune responses with substantial cross-reactivity and protective efficacy against other arthritogenic alphaviruses. Our findings also highlight the potential for development of a multi-virus targeting vaccine against alphaviruses with endemic and epidemic potential in the Americas.<br />Author summary Mayaro virus is an understudied alphavirus that is currently circulating in tropical environments in South and Central America without an approved vaccine. Recent outbreaks have suggested a broadening range and higher likelihood of urban outbreaks, increasing the public health risk. Mayaro virus is closely related to other arthritogenic alphaviruses with overlapping circulation such as chikungunya and Una viruses, both of which also lack clinically approved vaccines. Identification of a safe, easily manufactured, and effective strategy to vaccinate at risk populations is important to control outbreak potential. Here we report on a vaccination approach using a non-replicating adenovirus viral vector that encodes Mayaro virus structural proteins that assemble into non-infectious virus-like particles upon expression following vaccination. These particles stimulate strong immune responses against Mayaro virus. Upon testing against other alphaviruses, it was determined that the vaccine elicits cross-reactive neutralizing antibodies against chikungunya and Una viruses, significantly diminishes disease severity, and protects immunocompromised, highly susceptible mice from death following viral challenge. Our study provides new approaches to protect against these co-circulating viruses using a single vaccine. This approach is highly amenable to other virus targets for vaccine development and its ability to provide protection against chikungunya virus has global ramifications.
- Subjects :
- 0301 basic medicine
RNA viruses
Male
Viral Diseases
Adenoviruses
Physiology
viruses
Cross Protection
RC955-962
Pathology and Laboratory Medicine
Antibodies, Viral
Biochemistry
Mice
0302 clinical medicine
Medical Conditions
Arctic medicine. Tropical medicine
Immune Physiology
Medicine and Health Sciences
Medicine
Public and Occupational Health
Enzyme-Linked Immunoassays
Booster Doses
Vaccines
Immune System Proteins
Chikungunya Virus
biology
Viral Vaccine
virus diseases
Vaccination and Immunization
Vaccination
Infectious Diseases
Medical Microbiology
Viral Pathogens
Viruses
Female
Viral disease
Public aspects of medicine
RA1-1270
Pathogens
Genetic Engineering
Research Article
Neglected Tropical Diseases
Infectious Disease Control
Alphaviruses
030231 tropical medicine
Immunology
Genetic Vectors
Viremia
Alphavirus
Research and Analysis Methods
Microbiology
Virus
Antibodies
Adenoviridae
Togaviruses
03 medical and health sciences
Immune system
Virology
Animals
Immunoassays
Microbial Pathogens
business.industry
Public Health, Environmental and Occupational Health
Organisms
Biology and Life Sciences
Proteins
Chikungunya Infection
Viral Vaccines
biology.organism_classification
medicine.disease
Tropical Diseases
Antibodies, Neutralizing
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Immunization
Immunologic Techniques
Chikungunya Fever
Preventive Medicine
business
DNA viruses
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 15
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....83ed7e3ca4f96703101532b11f087d07