H7N9 live attenuated influenza vaccine in healthy adults: a randomised, double-blind, placebo-controlled, phase 1 trial

Rudenko, Larisa; Naykhin, Anatoly; Kiseleva, Irina; Stukova, Marina; Ерофеева, М. К.; Korenkov, Daniil; Matyushenko, Victoria; Sparrow, Erin; Kiény, Marie-Paule

doi:10.1016/s1473-3099(15)00378-3

Cited by 37 publications

(45 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These phenomena may possibly due to pre-existing immunogenicity at mucosal sites (7,29,30). Less than half of the vaccinees in a recent phase I clinical trial assessing safety and immunogenicity of a H7N9 LAIVs seroconverted (48%, (95% CI 29 4-67 5)) after one vaccination (31).…”

Section: Prime-boost Vaccinated Mice Intranasally Challenged With DIVmentioning

confidence: 99%

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Chinnakannan

Mullarkey

Ulaszewska

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

Abstract:Seasonal influenza viruses (IAV) are a common cause of acute respiratory illness worldwide and generate a significant socio-economic burden. IAV rapidly mutate, necessitating annual vaccine reformulation as traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality as compared to seasonal strains. Ongoing strategies to improve vaccine efficacy typically focus on providing broad-spectrum immunity, and while both B and T cells can mediate heterosubtypic responses, typical vaccine development will augment either humoral or cellular immunity. However, multipronged approaches, targeting several antigens, may limit the generation of viral escape mutants. There are few vaccine platforms that can deliver multiple antigens and generate robust cellular and humoral immunity. In this work, we describe a novel vaccination strategy, tested pre-clinically in mice, for the delivery of novel bivalent viral-vectored vaccines. Here, we show this strategy elicits potent T cell responses toward highly conserved internal antigens, whilst simultaneously inducing high levels of antibodies towards hemagglutinin (HA). Importantly, these humoral responses generate longlived plasma cells and generate antibodies capable of neutralising variant HA-expressing pseudotyped lentiviruses. Significantly, these novel viral-vectored vaccines induce strong immune responses capable of conferring protection in a stringent influenza A virus challenge.Thus, this vaccination regimen induces lasting efficacy toward influenza. Importantly, the simultaneous delivery of dual antigens may alleviate the selective pressure thought to potentiate antigenic diversity in avian influenza viruses.

show abstract

Section: Prime-boost Vaccinated Mice Intranasally Challenged With DIVmentioning

confidence: 99%

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Chinnakannan

Mullarkey

Ulaszewska

et al. 2017

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The two-dose immunization schedule resulted in measurable serum and local antibody production, and generation of CD4 + and CD8 + memory T cells. The results of the clinical trials were published [4], [17], [18], [19], [20].In 2009, GPO produced H1N1pdm LAIV, conducted preclinical and clinical trials, and registered the vaccine in Thailand. The work for preparation and registration of H5N2 pre-pandemic vaccine is in progress.…”

Section: Discussionmentioning

confidence: 99%

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Rudenko

Yeolekar

Kiseleva

et al. 2016

Vaccine

Self Cite

View full text Add to dashboard Cite

show abstract

“…H7N9 LAIV reassortant virus with a 6:2 genome composition (H7N9 LAIV 6:2) was prepared by classical reassortment in eggs and was tested in preclinical and clinical trials (de Jonge et al, 2016; Rudenko et al, 2016). This virus possesses the HA and NA genes of wild-type ( wt ) A/Anhui/1/2013 (H7N9) strain; the remaining genes come from A/Leningrad/134/17/57 (H2N2) MDV.…”

Section: Methodsmentioning

confidence: 99%

Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model

et al. 2017

Self Cite

View full text Add to dashboard Cite

This study sought to improve an existing live attenuated influenza vaccine (LAIV) by including nucleoprotein (NP) from wild-type virus rather than master donor virus (MDV). H7N9 LAIV reassortants with 6:2 (NP from MDV) and 5:3 (NP from wild-type virus) genome compositions were compared with regard to their growth characteristics, induction of humoral and cellular immune responses in mice, and ability to protect mice against homologous and heterologous challenge viruses. Although, in general, the 6:2 reassortant induced greater cell-mediated immunity in C57BL6 mice than the 5:3 vaccine, mice immunized with the 5:3 LAIV were better protected against heterologous challenge. The 5:3 LAIV-induced CTLs also had better in vivo killing activity against target cells loaded with the NP366 epitope of recent influenza viruses. Modification of the genome of reassortant vaccine viruses by incorporating the NP gene from wild-type viruses represents a simple strategy to improve the immunogenicity and cross-protection of influenza vaccines.

show abstract

H7N9 live attenuated influenza vaccine in healthy adults: a randomised, double-blind, placebo-controlled, phase 1 trial

Cited by 37 publications

References 31 publications

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model

Contact Info

Product

Resources

About