Development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes

Stobart, Christopher C.; Moore, Martin L.

doi:10.1586/14760584.2015.1095096

Cited by 3 publications

(5 citation statements)

References 126 publications

(102 reference statements)

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“…The significant time gap between pathogen emergence and vaccine licensure, could potentially lead to antigenic drift. There is potential that modern biotechnologies could be utilized to design novel vaccine platforms ( 251 , 271 , 272 ). Clinically derived recombinant MuV lacking the expression of the immunomodulatory V or SH protein are currently being investigated ( 273 ).…”

Section: Laboratory Determinants Of An Effective Immune Response To Mmentioning

confidence: 99%

“…Vaccine RIT 4385 strain derived from one of the two distinct virus subtypes of the JL vaccine (JL5) showed comparable seroconversion rates despite inducing a significantly lower geometric mean antibody titer when compared to recipients of the JL vaccine, but does not have any longitudinal trials investigating its efficacy, even though there are populations who are currently receiving it (101,270).…”

Section: Development Of Improved Vaccinesmentioning

confidence: 99%

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Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

Connell

Leahy

et al. 2020

Front. Immunol.

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History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity.

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Section: Laboratory Determinants Of An Effective Immune Response To Mmentioning

confidence: 99%

Section: Development Of Improved Vaccinesmentioning

confidence: 99%

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

Connell

Leahy

et al. 2020

Front. Immunol.

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“…An alternative approach to the design of attenuated viruses as vaccine candidates that several laboratories have followed is the identification of virulence-associated viral genes (DeDiego et al, 2014a;Stobart and Moore, 2015;Totura and Baric, 2012) that, in many cases, encode nonessential immunomodulatory proteins. Modification or deletion of these genes leads to the generation of attenuated viruses that may be useful as vaccine candidates.…”

Section: Strategies To Engineer Attenuated Covs As Vaccine Candidatesmentioning

confidence: 99%

“…Our laboratory has used this strategy extensively to generate CoV vaccines. Also, other groups have used this approach successfully to produce vaccine candidates for influenza, respiratory syncytial virus, measles, dengue, and mumps (Kirkpatrick et al, 2016;Stobart and Moore, 2015). Engineering attenuated CoVs as vaccine candidates requires the availability of reverse-genetics systems suitable to introduce deletions of (or mutations in) virulence genes as well as appropriate animal models for the evaluation of efficacy and safety of these candidate vaccines.…”

Section: Strategies To Engineer Attenuated Covs As Vaccine Candidatesmentioning

confidence: 99%

Molecular Basis of Coronavirus Virulence and Vaccine Development

Enjuanes

Zúñiga

Castaño-Rodríguez

et al. 2016

Advances in Virus Research

149

141

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Virus vaccines have to be immunogenic, sufficiently stable, safe, and suitable to induce long-lasting immunity. To meet these requirements, vaccine studies need to provide a comprehensive understanding of (i) the protective roles of antiviral B and T-cell-mediated immune responses, (ii) the complexity and plasticity of major viral antigens, and (iii) virus molecular biology and pathogenesis. There are many types of vaccines including subunit vaccines, whole-inactivated virus, vectored, and live-attenuated virus vaccines, each of which featuring specific advantages and limitations. While nonliving virus vaccines have clear advantages in being safe and stable, they may cause side effects and be less efficacious compared to live-attenuated virus vaccines. In most cases, the latter induce long-lasting immunity but they may require special safety measures to prevent reversion to highly virulent viruses following vaccination. The chapter summarizes the recent progress in the development of coronavirus (CoV) vaccines, focusing on two zoonotic CoVs, the severe acute respiratory syndrome CoV (SARS-CoV), and the Middle East respiratory syndrome CoV, both of which cause deadly disease and epidemics in humans. The development of attenuated virus vaccines to combat infections caused by highly pathogenic CoVs was largely based on the identification and characterization of viral virulence proteins that, for example, interfere with the innate and adaptive immune response or are involved in interactions with specific cell types, such as macrophages, dendritic and epithelial cells, and T lymphocytes, thereby modulating antiviral host responses and viral pathogenesis and potentially resulting in deleterious side effects following vaccination.

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“…Thus, understanding the mechanisms of viral attenuation will hopefully provide a simple and universal way to vaccine development. In fact, codon deoptimization has been attempted in the development of live attenuated Influenza A and respiratory virus vaccines (Nogales et al, 2014 ; Cox et al, 2015 ; Fan et al, 2015 ; Stobart and Moore, 2015 ). However, these innovative approaches in vaccine development have been not widely explored and fundamental research is urgently required in parallel to further understand the mechanisms of viral attenuation.…”

Section: Discussionmentioning

confidence: 99%

Incompatible Translation Drives a Convergent Evolution and Viral Attenuation During the Development of Live Attenuated Vaccine

Wang

Mao

et al. 2018

Front. Cell. Infect. Microbiol.

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Live attenuated vaccines are widely used to protect humans or animals from pathogen infections. We have previously developed a chicken embryo-attenuated Duck Hepatitis A Virus genotype 1 (DHAV-1) vaccine (CH60 strain). This study aims to understand the mechanisms that drive a virulent strain to an attenuated virus. Here, we systematically compared five DHAV-1 chicken embryo attenuated strains and 68 virulent strains. Phylogenetic analysis indicated that duck virulent strains isolated from different geographic regions of China undergo a convergent evolution in the chicken embryos. Comparative analysis indicated that the codon usage bias of the attenuated strains were shaped by chicken codons usage bias, which essentially contributed to viral adaption in the unsuitable host driven by incompatible translation. Of note, the missense mutations in coding region and mutations in untranslated regions may also contribute to viral attenuation of DHAV-1 to some extent. Importantly, we have experimentally confirmed that the expression levels of four viral proteins (2A3pro, 2A3pro, 3Cpro, and 3Dpro) in the liver and kidney of ducks infected with an attenuated strain are significantly lower than that infected with a virulent strain, despite with similar virus load. Thus, the key mechanisms of viral attenuation revealed by this study may lead to innovative and easy approaches in designing live attenuated vaccines.

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Development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes

Cited by 3 publications

References 126 publications

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines?

Molecular Basis of Coronavirus Virulence and Vaccine Development

Incompatible Translation Drives a Convergent Evolution and Viral Attenuation During the Development of Live Attenuated Vaccine

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