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The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation.

ABSTRACT: The human immune response to eastern equine encephalitis virus (EEEV) infection is poorly characterized due to the rarity of infection. We examined the humoral and cellular immune response to EEEV acquired from an infected donor via liver transplantation. Both binding and highly neutralizing antibodies to EEEV as well as a robust EEEV-specific IgG memory B cell response were generated. Despite triple-drug immunosuppressive therapy, a virus-specific CD4+ T cell response, predominated by interferon-? production, was generated. T cell epitopes on the E2 envelope protein were identified by interferon-? ELISpot. Although these results are from a single person who acquired EEEV by a non-traditional mechanism, to our knowledge this work represents the first analysis of the human cellular immune response to EEEV.

SUBMITTER: Raabe V

PROVIDER: S-EPMC7541818 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation.

Raabe Vanessa V Lai Lilin L Xu Yong Y Huerta Chris C Wang Dongli D Pouch Stephanie M SM Burke Crystal W CW Piper Ashley E AE Gardner Christina L CL Glass Pamela J PJ Mulligan Mark J MJ

Frontiers in microbiology 20200924

The human immune response to eastern equine encephalitis virus (EEEV) infection is poorly characterized due to the rarity of infection. We examined the humoral and cellular immune response to EEEV acquired from an infected donor via liver transplantation. Both binding and highly neutralizing antibodies to EEEV as well as a robust EEEV-specific IgG memory B cell response were generated. Despite triple-drug immunosuppressive therapy, a virus-specific CD4+ T cell response, predominated by interfero ...[more]

PMID: 33072022

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Project description:Background: Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus that is primarily found in North America and the Caribbean. Over the past decade there has been an increase in virus activity, including large outbreaks in human and horse populations. Predicted climate change is expected to affect the range of mosquitoes including vectors of EEEV, which may alter disease risk posing a public health concern. Methods: A scoping review (ScR) was conducted to identify and characterize the global evidence on EEEV. A thorough search was conducted in relevant bibliographic databases and government websites. Two reviewers screened titles and abstracts for relevance and the characteristics of relevant articles were extracted using a uniformly implemented data collection form. The study protocol was developed a priori and described the methods and tools used and this article follows the PRISMA-ScR guidelines for reporting ScRs. Results: The ScR included 718 relevant research articles. The majority of the articles originated from North America (97%) between 1933 and 2019. EEEV has been identified in 35 species of mosquitoes, over 200 species of birds, various domestic animals, wild mammals, reptiles, and amphibians. Articles identified in this ScR primarily covered three topic areas: epidemiology of hosts and vectors (344 articles) including surveillance results (138), pathogenesis of EEEV in hosts (193), and in vitro studies characterizing EEEV (111). Fewer articles evaluated the accuracy of diagnostic tests (63), the efficacy of mitigation strategies (62), transmission dynamics (56), treatment of EEEV in hosts (10), societal knowledge, attitudes, and perceptions (4), and economic burden (2). Conclusion: With the projected impact of climate change on mosquito populations, it is expected that the risk of EEEV could change resulting in higher disease burden or spread into previously unaffected areas. Future research efforts should focus on closing some of the important knowledge gaps identified in this ScR.

Project description:Live attenuated vaccines (LAVs), if sufficiently safe, provide the most potent and durable anti-pathogen responses in vaccinees with single immunizations commonly yielding lifelong immunity. Historically, viral LAVs were derived by blind passage of virulent strains in cultured cells resulting in adaptation to culture and a loss of fitness and disease-causing potential in vivo. Mutations associated with these phenomena have been identified but rarely have specific attenuation mechanisms been ascribed, thereby limiting understanding of the attenuating characteristics of the LAV strain and applicability of the attenuation mechanism to other vaccines. Furthermore, the attenuated phenotype is often associated with single nucleotide changes in the viral genome, which can easily revert to the virulent sequence during replication in animals. Here, we have used a rational approach to attenuation of eastern equine encephalitis virus (EEEV), a mosquito-transmitted alphavirus that is among the most acutely human-virulent viruses endemic to North America and has potential for use as an aerosolized bioweapon. Currently, there is no licensed antiviral therapy or vaccine for this virus. Four virulence loci in the EEEV genome were identified and were mutated individually and in combination to abrogate virulence and to resist reversion. The resultant viruses were tested for virulence in mice to examine the degree of attenuation and efficacy was tested by subcutaneous or aerosol challenge with wild type EEEV. Importantly, all viruses containing three or more mutations were avirulent after intracerebral infection of mice, indicating a very high degree of attenuation. All vaccines protected from subcutaneous EEEV challenge while a single vaccine with three mutations provided reproducible, near-complete protection against aerosol challenge. These results suggest that informed mutation of virulence determinants is a productive strategy for production of LAVs even with highly virulent viruses such as EEEV. Furthermore, these results can be directly applied to mutation of analogous virulence loci to create LAVs from other viruses.

Dataset Information

The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation.

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The Immune Response to Eastern Equine Encephalitis Virus Acquired Through Organ Transplantation.

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