Insights into current clinical research on the immunogenicity of live attenuated influenza vaccines

Isakova–Sivak, Irina; Grigorieva, Elena

doi:10.1080/14760584.2020.1711056

Cited by 13 publications

(10 citation statements)

References 110 publications

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“…Here, we explored the possibility of licensed live attenuated influenza vaccine backbone as a viral vector to deliver additional conserved M2e epitopes of influenza A viruses to the target cells to enhance the breadth of protection afforded by classical LAIV viruses. It is well known that LAIVs induce cross-reactive immunity with a potential to protect against drifted influenza viruses in a variety of animal models as well as in human trials [15,[42][43][44], and numerous studies have proven that LAIV is a promising viral vector for designing vaccines against other infectious pathogens [45][46][47][48]. Our recent study demonstrated that seasonal H1N1 and H3N2 LAIVs expressing four M2e tandem repeats within the chimeric HAs can elicit M2e-specific antibody and, to a lesser extent, T-cell responses which enhanced cross-protective potential of the vaccines [14].…”

Section: Discussionmentioning

confidence: 99%

A Strategy to Elicit M2e-Specific Antibodies Using a Recombinant H7N9 Live Attenuated Influenza Vaccine Expressing Multiple M2e Tandem Repeats

et al. 2021

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Influenza viruses remain a serious public health problem. Vaccination is the most effective way to prevent the disease; however, seasonal influenza vaccines demonstrate low or no effectiveness against antigenically drifted and newly emerged influenza viruses. Different strategies of eliciting immune responses against conserved parts of various influenza virus proteins are being developed worldwide. We constructed a universal live attenuated influenza vaccine (LAIV) candidate with enhanced breadth of protection by modifying H7N9 LAIV by incorporating four epitopes of M2 protein extracellular part into its hemagglutinin molecule. The new recombinant H7N9+4M2e vaccine induced anti-M2e antibody responses and demonstrated increased protection against heterosubtypic challenge viruses in direct and serum passive protection studies, compared to the classical H7N9 LAIV. The results of our study suggest that the H7N9+4M2e warrants further investigation in pre-clinical and phase 1 clinical trials.

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Section: Discussionmentioning

confidence: 99%

A Strategy to Elicit M2e-Specific Antibodies Using a Recombinant H7N9 Live Attenuated Influenza Vaccine Expressing Multiple M2e Tandem Repeats

et al. 2021

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“…These data suggest that the site of administration of T-cell-based RSV vaccines is crucial. For example, these epitopes can be delivered to the respiratory tract by live attenuated influenza vaccine (LAIV) viruses (Isakova-Sivak et al, 2016a), which are known to be effective inducers of cross-reactive T-cell responses (Isakova-Sivak et al, 2020;Korenkov et al, 2018;Mohn et al, 2017). In addition, such bivalent LAIV-RSV vaccines could be used for simultaneous prophylaxis of the two respiratory pathogens.…”

Section: Introductionmentioning

confidence: 99%

Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses

et al. 2020

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“…On the other hand, the suppression of influenza A replication by influenza B NP has been found [59]. The lower variability of influenza B could provide a cross-reactivity of immunity factors and consequently a faster immunity activation after boost with a new vaccine dose; this is discussed as a possible reason for the low vaccine effectiveness of the influenza A component (reviewed in [60]). The ability to prepare strains of both subtypes on the one backbone, in theory, could be a key to solving the interference problem.…”

Section: Discussionmentioning

confidence: 99%

Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model

et al. 2021

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Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required.

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Insights into current clinical research on the immunogenicity of live attenuated influenza vaccines

Cited by 13 publications

References 110 publications

A Strategy to Elicit M2e-Specific Antibodies Using a Recombinant H7N9 Live Attenuated Influenza Vaccine Expressing Multiple M2e Tandem Repeats

A Strategy to Elicit M2e-Specific Antibodies Using a Recombinant H7N9 Live Attenuated Influenza Vaccine Expressing Multiple M2e Tandem Repeats

Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses

Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model

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