Protective #immunity by an engineered #DNA #vaccine for #Mayaro virus (PLoS Negl Trop Dis., abstract)

[Source: PLoS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Protective immunity by an engineered DNA vaccine for Mayaro virus

Hyeree Choi, Sagar B. Kudchodkar, Emma L. Reuschel, Kanika Asija, Piyush Borole, Michelle Ho, Krzysztof Wojtak, Charles Reed, Stephanie Ramos, Nathen E. Bopp, Patricia V. Aguilar, Scott C. Weaver, J. Joseph Kim,  [ … ], Kar Muthumani

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Published: February 7, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007042

 

Abstract

Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.

 

Author summary

Mayaro virus (MAYV) is a mosquito-transmitted virus that causes fever, headache, chills, nausea and joint pain that can last for months after infection. The rising number of cases, due to increased mosquito circulation, and the threat of an epidemic emphasize its importance as an emerging virus, but there are no licensed vaccines to prevent Mayaro infection nor therapeutics to treat it. In this study, we gathered fundamental knowledge on how the immune system responds to MAYV infection, and we evaluated the efficacy of a novel, synthetic DNA envelope vaccine (scMAYV-E) in mice. Analysis of immune responses in mice demonstrated that this vaccine induces potent T cell immunity and antibodies. Mice who receive the vaccine and then are challenged with live MAYV are protected against Mayaro disease. This data provides evidence that the DNA-based MAYV vaccine may be able to prevent Mayaro disease. Thus, the scMAYV-E vaccine is a promising step forward for MAYV vaccine development. Future testing will evaluate whether this vaccine is a viable means to halt the spread of MAYV and protect individuals from Mayaro disease.

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Citation: Choi H, Kudchodkar SB, Reuschel EL, Asija K, Borole P, Ho M, et al. (2019) Protective immunity by an engineered DNA vaccine for Mayaro virus. PLoS Negl Trop Dis 13(2): e0007042. https://doi.org/10.1371/journal.pntd.0007042

Editor: Kenneth E. Olson, Colorado State University, UNITED STATES

Received: April 16, 2018; Accepted: November 30, 2018; Published: February 7, 2019

Copyright: © 2019 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: KM and DBW note funding by Inovio Pharmaceuticals, PA, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: CCR, SR, LH, and JJK are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options. KM discloses grant funding, industry collaborations, speaking honoraria, and fees for consulting. He has received consulting fees from Inovio Pharmaceuticals related to DNA vaccine development. He has a patent application for DNA vaccine development and delivery of DNA encoded monoclonal antibodies pending to Inovio Pharmaceuticals. Remuneration includes direct payments. DBW is the W.W. Smith Charitable Trust Professor in Cancer Research at the Wistar Institute. DBW discloses grant funding, SAB and Board service, industry collaborations, speaking honoraria, and fees for consulting. His service includes serving on scientific review committees and advisory boards. Remuneration includes direct payments and/or stock or stock options. He notes potential conflicts associated with this work with Pfizer, Bristol Myers Squibb, Inovio Pharmaceuticals, Merck, VGXI, Geneos, Astrazeneca and potentially others. Licensing of technology from this laboratory has created over 150 jobs in the biotech/pharma industry. The other authors declare no competing financial interests.

Keywords: Alphavirus; Mayaro virus; Vaccines; Animal models.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.