H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses

Mahmood, Kutubuddin; Bright, Rick A.; Mytle, Nutan; Carter, Donald M.; Crevar, Corey J.; Achenbach, Jenna E.; Heaton, Penny M.; Tumpey, Terrence M.; Ross, Ted M.

doi:10.1016/j.vaccine.2008.07.084

Cited by 116 publications

(84 citation statements)

References 8 publications

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“…The HAI titers and cross-clade reactivity of sera in the human trial are in agreement with the preclinical studies involving ferrets and a similar VLP vaccine product (30). The H5N1 VLP vaccine was immunogenic, and the HAI titers were comparable to those reported with an inactivated egg-derived More recently, a VLP vaccine against the pandemic H1N1 strain was evaluated in the Mexican population and was found to be safe and immunogenic (27).…”

Section: Discussionsupporting

confidence: 80%

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H5N1 Virus-Like Particle Vaccine Elicits Cross-Reactive Neutralizing Antibodies That Preferentially Bind to the Oligomeric Form of Influenza Virus Hemagglutinin in Humans

Khurana

Verma

et al. 2011

J Virol

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Section: Discussionsupporting

confidence: 80%

“…Furthermore, VLPs present the key antigenic targets of influenza virus, HA and NA, in a native-like conformation similar to the intact virion. Studies in animal models also provided evidence for generation of cross-clade protective antibodies following H5N1 VLP (but not rHA) immunization (4,5,30,38).…”

Section: Discussionmentioning

confidence: 99%

H5N1 Virus-Like Particle Vaccine Elicits Cross-Reactive Neutralizing Antibodies That Preferentially Bind to the Oligomeric Form of Influenza Virus Hemagglutinin in Humans

Khurana

Verma

et al. 2011

J Virol

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“…Ferrets were vaccinated intranasally twice on days 0 and 14 with 10 6 EID 50 of virus/animal and challenged at 2 weeks postboost with 10 6 EID 50 of H5N1. This challenge was extremely severe (equivalent to 10,000 times the 50% ferret lethal dose [ 27]) and was chosen with the objective to discriminate the protective responses induced by the H9N2-H5 vector from the cross-protection induced by the H9N2-GFP vector control. Following challenge, PBS-vaccinated animals had high levels of viral replication (Fig.…”

Section: Fig 1 Rearranged H9n2 Influenza a Viruses Expressing Foreignmentioning

confidence: 99%

Influenza Viruses with Rearranged Genomes as Live-Attenuated Vaccines

Pena

Sutton

Chockalingam

et al. 2013

J Virol

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“…Influenza VLPs are noninfectious particles that mimic the virus in structure and morphology, can be produced using an egg-free cell culture system, and have been shown to be highly immunogenic, inducing protective immunity (9,15,19,27,35,41,42,44). Most current vaccines are administered intramuscularly to humans in liquid formulations using hypodermic needles or syringes.…”

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confidence: 99%

Intradermal Vaccination with Influenza Virus-Like Particles by Using Microneedles Induces Protection Superior to That with Intramuscular Immunization

Quan

Kim

Vunnava

et al. 2010

J Virol

114

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Influenza virus-like particles (VLPs) are a promising cell culture-based vaccine, and the skin is considered an attractive immunization site. In this study, we examined the immunogenicity and protective efficacy of influenza VLPs (H1N1 A/PR/8/34) after skin vaccination using vaccine dried on solid microneedle arrays. Coating of microneedles with influenza VLPs using an unstabilized formulation was found to decrease hemagglutinin (HA) activity, whereas inclusion of trehalose disaccharide preserved the HA activity of influenza VLP vaccines after microneedles were coated. Microneedle vaccination of mice in the skin with a single dose of stabilized influenza VLPs induced 100% protection against challenge infection with a high lethal dose. In contrast, unstabilized influenza VLPs, as well as intramuscularly injected vaccines, provided inferior immunity and only partial protection (<40%). The stabilized microneedle vaccination group showed IgG2a levels that were 1 order of magnitude higher than those of other groups and had the lowest lung viral titers after challenge. Also, levels of recall immune responses, including hemagglutination inhibition titers, neutralizing antibodies, and antibody-secreting plasma cells, were significantly higher after skin vaccination with stabilized formulations. Therefore, our results indicate that HA stabilization, combined with vaccination via the skin using a vaccine formulated as a solid microneedle patch, confers protection superior to that with intramuscular injection and enables potential dose-sparing effects which are reflected by pronounced increases in rapid recall immune responses against influenza virus.

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H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses

Cited by 116 publications

References 8 publications

H5N1 Virus-Like Particle Vaccine Elicits Cross-Reactive Neutralizing Antibodies That Preferentially Bind to the Oligomeric Form of Influenza Virus Hemagglutinin in Humans

H5N1 Virus-Like Particle Vaccine Elicits Cross-Reactive Neutralizing Antibodies That Preferentially Bind to the Oligomeric Form of Influenza Virus Hemagglutinin in Humans

Influenza Viruses with Rearranged Genomes as Live-Attenuated Vaccines

Intradermal Vaccination with Influenza Virus-Like Particles by Using Microneedles Induces Protection Superior to That with Intramuscular Immunization

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