A single cycle influenza virus coated in H7 haemagglutinin generates neutralizing antibody responses to haemagglutinin and neuraminidase glycoproteins and protection from heterotypic challenge

Powell, Timothy J.; Rijal, Pramila; McEwen-Smith, Rosanna M.; Byun, Hyun; Schimanski, Lisa; Huang, Kuan-Ying A.; Daniels, Rodney S.; Townsend, Alain

doi:10.1099/jgv.0.001228

Cited by 8 publications

(13 citation statements)

References 64 publications

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“…For infections using non-fluorescent influenza virus, we used the A/HK-x31 (x31, H3N2) strain. The reporter strains expressing GFP (GFP-S-Flu; [S-eGFP/N1(PR8)]) or CFP (CFP-S-Flu; [S-eCFP/N1(PR8)]) were generated using the Cambridge strain of A/Puerto Rico/8/34 ( Powell et al., 2012 , 2019 ). The viruses used were cloned and propagated in-house.…”

Section: Methodsmentioning

confidence: 99%

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Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites

et al. 2022

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Section: Methodsmentioning

confidence: 99%

“…Single-cycle fluorescent reporter strain of influenza A virus was prepared as previously described ( Powell et al., 2012 , 2019 ). Briefly, plasmids encoding eCFP with SapI restriction sites were synthesised by GeneArt and cloned into the pPoll vector.…”

Section: Methodsmentioning

confidence: 99%

Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites

et al. 2022

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“…Taken together, these findings indicate that the mechanisms of protection in mice and pigs may differ. This is supported by studies with another broadly protective influenza vaccine candidate, S-FLU, which induced heterotypic protection in mice and ferrets against a heterologous virus, while in the pigs, only lung pathology was reduced but not viral shedding (21,26,28). Cross-reactive immunity could be due not only to T cell responses to conserved internal antigens but also to antibodies to conserved epitopes of the haemagglutinin (HA) and neuraminidase (NA) (43).…”

Section: Discussionmentioning

confidence: 87%

“…Determination of end point titer ELISAs and microneutralization (MN) assays on BAL and serum samples were performed using standard procedures ( 26 – 28 ). pH1N1 or H3N2 virus or recombinant hemagglutinin (HA) (1 µg/ml) protein from A/England/195/2009 (HA), H3 from A/Hong Kong/5738/14 (H3N2), H5 from A/ty/Turkey/1/05 (H5N1) provided by Alain Townsend (University of Oxford) or H7 from A/ty/Italy/984/00 (H7N1), provided by Florian Krammer (Mount Sinai), were coated overnight on 96-well microtiter plates (Nunc MaxiSorp, Sigma Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model

et al. 2023

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T cell responses directed against highly conserved viral proteins contribute to the clearance of the influenza virus and confer broadly cross-reactive and protective immune responses against a range of influenza viruses in mice and ferrets. We examined the protective efficacy of mucosal delivery of adenoviral vectors expressing hemagglutinin (HA) and nucleoprotein (NP) from the H1N1 virus against heterologous H3N2 challenge in pigs. We also evaluated the effect of mucosal co-delivery of IL-1β, which significantly increased antibody and T cell responses in inbred Babraham pigs. Another group of outbred pigs was first exposed to pH1N1 as an alternative means of inducing heterosubtypic immunity and were subsequently challenged with H3N2. Although both prior infection and adenoviral vector immunization induced strong T-cell responses against the conserved NP protein, none of the treatment groups demonstrated increased protection against the heterologous H3N2 challenge. Ad-HA/NP+Ad-IL-1β immunization increased lung pathology, although viral load was unchanged. These data indicate that heterotypic immunity may be difficult to achieve in pigs and the immunological mechanisms may differ from those in small animal models. Caution should be applied in extrapolating from a single model to humans.

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“…NY-ESO-1 S-FLU (X31) was generated by infecting MDCK-SIAT1 stably transfected with X31 H3 (MDCK-X31) with the NY-ESO-1 S-FLU (PR8) seed virus (approximately multiplicity of infection [MOI] 0.01) and the supernatant was harvested as described above after 48 hr. NY-ESO-1 S-FLU was titrated as TCID50 as previously described ( Powell et al, 2012 ; Powell et al, 2019 ). In brief, supernatant containing NY-ESO-1 S-FLU was titrated in 1/2-log serial dilution in VGM (total 50 µl) across a flat-bottom 96-well plate seeded with 3e4 MDCK-PR8 or MDCK-X31 cells.…”

Section: Methodsmentioning

confidence: 99%

Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors

Kandasamy

Gileadi

Rijal

et al. 2023

eLife

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Virus-based tumour vaccines offer many advantages compared to other antigen-delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+ T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (NY-ESO-1 S-FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1-specific CD8+ T cell response in lungs and spleen that resulted in the regression of NY-ESO-1-expressing lung tumour and subcutaneous tumour, respectively. Combined administration with anti-PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen-specific CD8+ T cell response and protection against tumour development in combination with PD-1 blockade.

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A single cycle influenza virus coated in H7 haemagglutinin generates neutralizing antibody responses to haemagglutinin and neuraminidase glycoproteins and protection from heterotypic challenge

Cited by 8 publications

References 64 publications

Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites

Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites

Effect of mucosal adjuvant IL-1β on heterotypic immunity in a pig influenza model

Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors

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