Evaluation of A(H1N1)pdm09 LAIV vaccine candidates stability and replication efficiency in primary human nasal epithelial cells

Shcherbik, Svetlana; Pearce, Nicholas; Carney, P.J.; Bazhenova, Ekaterina; Larionova, Natalie; Kiseleva, Irina; Rudenko, Larisa; Kumar, Amrita; Goldsmith, Cynthia S.; Dugan, Vivien G.; Stevens, James; Wentworth, David E.; Bousse, Tatiana

doi:10.1016/j.jvacx.2019.100031

Cited by 11 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phenotypic (cold adaptation and temperature sensitivity) and genotypic analyses conducted on the viruses recovered from the study subjects suggest that the vaccine is genetically stable after in vivo passage. These data confirmed our previous findings that not only seasonal, but also pandemic and potential pandemic LAIVs on an L17 MDV backbone are genetically and phenotypically stable after replication in humans [58][59][60][61].…”

Section: Discussionsupporting

confidence: 91%

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

et al. 2020

Self Cite

View full text Add to dashboard Cite

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted.

show abstract

Section: Discussionsupporting

confidence: 91%

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…For a virus with chimeric HA, this test can give information regarding the functionality of its HA structure. Our results suggest that the chimeric A/B virus has significant HA thermostability: its hemagglutinating activity was retained even after treatment at 60 °C ( Table 2 ), whereas nonstable viruses lose their HA activity after exposure to 52–56 °C [ 37 , 39 ]. Importantly, the thermostability of the H2B chimeric virus was close to that of the B/Brisbane/60/08 virus, the source of the HA ectodomain, and the full-length NA of the A/B chimera.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Successful replication of LAIV in nasal epithelia appears to be a prerequisite for facilitating antigen presentation by the major histocompatibility complex-I (MHC-I) to activate CD8 + T cells for effective viral clearance [ 3 , 18 , 85 ]. The thermal instability of H1N1 LAIV strain (A/California/07/2009), causing its defective replication in human nasal cells [ 86 , 87 ], has been associated with reduced efficacy of LAIV against H1N1 virus [ 88 ]. Indeed, modification to a more stable, replication competent version of LAIV in subsequent influenza seasons (2017–2018) improved its efficacy [ 89 ].…”

Section: Impact Of Pre-existing Antibodies On T Cell Immunogenicitmentioning

confidence: 99%

Impact of Pre-Existing Immunity to Influenza on Live-Attenuated Influenza Vaccine (LAIV) Immunogenicity

et al. 2020

View full text Add to dashboard Cite

During the previous influenza seasons, between 2010 and 2016, the live attenuated influenza vaccine (LAIV) provided variable efficacy against influenza in the U.S., causing the recommendation against the use of the LAIV. In striking contrast, pre-clinical studies have repeatedly demonstrated superior efficacy of LAIV against mismatched influenza viruses, compared to inactivated influenza vaccines (IIV). This disparity in reported vaccine efficacies between pre-clinical and clinical studies may in part be explained by limitations of the animal models of influenza. In particular, the absence of pre-existing immunity in animal models has recently emerged as a potential explanation for the discrepancies between preclinical findings and human studies. This commentary focuses on the potential impact of pre-existing immunity on LAIV induced immunogenicity with an emphasis on cross-protective immunity.

show abstract

Evaluation of A(H1N1)pdm09 LAIV vaccine candidates stability and replication efficiency in primary human nasal epithelial cells

Cited by 11 publications

References 35 publications

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

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

Impact of Pre-Existing Immunity to Influenza on Live-Attenuated Influenza Vaccine (LAIV) Immunogenicity

Contact Info

Product

Resources

About