Live Attenuated Reassortant Vaccines Based on A/Leningrad/134/17/57 Master Donor Virus Against H5 Avian Influenza

Kiseleva, Irina; Larionova, Natalie; Rudenko, Larisa

doi:10.2174/1874285801711010316

Cited by 4 publications

(3 citation statements)

References 46 publications

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“…A tailored mosaic peptide vaccine might be the best way to circumvent influenza virus escape, but on a population level for vaccine rollout would be impractical considering HLA selection for full-length proteins and immune competition during T cell priming, this area of research needs further exploration. The H5-derived NP protein is already able to be interchanged in the Leningrad LAIV backbone, demonstrating the possibility of a mosaic approach to incorporating T cell peptide variants with current methods [ 190 ].…”

Section: Universal Vaccine May Still Need To Thwart Viral Escapementioning

confidence: 99%

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

et al. 2018

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Next-generation vaccines that utilize T cells could potentially overcome the limitations of current influenza vaccines that rely on antibodies to provide narrow subtype-specific protection and are prone to antigenic mismatch with circulating strains. Evidence from animal models shows that T cells can provide heterosubtypic protection and are crucial for immune control of influenza virus infections. This has provided hope for the design of a universal vaccine able to prime against diverse influenza virus strains and subtypes. However, multiple hurdles exist for the realisation of a universal T cell vaccine. Overall primary concerns are: extrapolating human clinical studies, seeding durable effective T cell resident memory (Trm), population human leucocyte antigen (HLA) coverage, and the potential for T cell-mediated immune escape. Further comprehensive human clinical data is needed during natural infection to validate the protective role T cells play during infection in the absence of antibodies. Furthermore, fundamental questions still exist regarding the site, longevity and duration, quantity, and phenotype of T cells needed for optimal protection. Standardised experimental methods, and eventually simplified commercial assays, to assess peripheral influenza-specific T cell responses are needed for larger-scale clinical studies of T cells as a correlate of protection against influenza infection. The design and implementation of a T cell-inducing vaccine will require a consensus on the level of protection acceptable in the community, which may not provide sterilizing immunity but could protect the individual from severe disease, reduce the length of infection, and potentially reduce transmission in the community. Therefore, increasing the standard of care potentially offered by T cell vaccines should be considered in the context of pandemic preparedness and zoonotic infections, and in combination with improved antibody vaccine targeting methods. Current pandemic vaccine preparedness measures and ongoing clinical trials under-utilise T cell-inducing vaccines, reflecting the myriad questions that remain about how, when, where, and which T cells are needed to fight influenza virus infection. This review aims to bring together basic fundamentals of T cell biology with human clinical data, which need to be considered for the implementation of a universal vaccine against influenza that harnesses the power of T cells.

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Section: Universal Vaccine May Still Need To Thwart Viral Escapementioning

confidence: 99%

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

et al. 2018

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“…There are two different types of live attenuated influenza vaccines (LAIV) commercially available, a quadrivalent vaccine, commercially known as FluMist ( Table 1 and Figure 2 ), which came in the market in 2003 in USA, and a trivalent vaccine created by the Institute of Experimental Medicine, St Petersburg, Russia. The Russian vaccine has been in the market for more than 50 years [ 173 , 174 ] and is based on cold–adapted A/Leningrad/134/17/57 (H2N2) (Len–MDV) and B/USSR/60/69 Master Donor Viruses (MDVs) with the addition of a circulating seasonal strain [ 175 ]. The quadrivalent vaccine is based on the “Ann Arbour” backbone (A/Ann Arbor/6/60 and B/Ann Arbor/1/66) and contains two B strains (B/Yamagata/16/88 and the B/Victoria/2/87 lineages), in addition to a A/H1N1 and a A/H3N2 strain [ 176 ].…”

Section: Nsv Vaccines On the Market Or Under Developmentmentioning

confidence: 99%

Investigating the Interaction between Negative Strand RNA Viruses and Their Hosts for Enhanced Vaccine Development and Production

et al. 2021

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The current pandemic has highlighted the ever-increasing risk of human to human spread of zoonotic pathogens. A number of medically-relevant zoonotic pathogens are negative-strand RNA viruses (NSVs). NSVs are derived from different virus families. Examples like Ebola are known for causing severe symptoms and high mortality rates. Some, like influenza, are known for their ease of person-to-person transmission and lack of pre-existing immunity, enabling rapid spread across many countries around the globe. Containment of outbreaks of NSVs can be difficult owing to their unpredictability and the absence of effective control measures, such as vaccines and antiviral therapeutics. In addition, there remains a lack of essential knowledge of the host–pathogen response that are induced by NSVs, particularly of the immune responses that provide protection. Vaccines are the most effective method for preventing infectious diseases. In fact, in the event of a pandemic, appropriate vaccine design and speed of vaccine supply is the most critical factor in protecting the population, as vaccination is the only sustainable defense. Vaccines need to be safe, efficient, and cost-effective, which is influenced by our understanding of the host–pathogen interface. Additionally, some of the major challenges of vaccines are the establishment of a long-lasting immunity offering cross protection to emerging strains. Although many NSVs are controlled through immunisations, for some, vaccine design has failed or efficacy has proven unreliable. The key behind designing a successful vaccine is understanding the host–pathogen interaction and the host immune response towards NSVs. In this paper, we review the recent research in vaccine design against NSVs and explore the immune responses induced by these viruses. The generation of a robust and integrated approach to development capability and vaccine manufacture can collaboratively support the management of outbreaking NSV disease health risks.

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“…There are several H5 vaccine candidates based on a master donor of influenza A virus (IAV), for example, H5N1, H5N2, H5N8, and other strains [14][15][16]. Some of these vaccines have been evaluated in clinical trials [17,18].…”

Section: Introductionmentioning

confidence: 99%

Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model

Sun

Wang

et al. 2021

Viruses

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H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.

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Live Attenuated Reassortant Vaccines Based on A/Leningrad/134/17/57 Master Donor Virus Against H5 Avian Influenza

Cited by 4 publications

References 46 publications

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

Harnessing the Power of T Cells: The Promising Hope for a Universal Influenza Vaccine

Investigating the Interaction between Negative Strand RNA Viruses and Their Hosts for Enhanced Vaccine Development and Production

Safety, Immunogenicity, and Protective Efficacy of an H5N1 Chimeric Cold-Adapted Attenuated Virus Vaccine in a Mouse Model

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