Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine

Muszkat, Mordechai; Greenbaum, Evgenia; Ben‐Yehuda, Arie; Oster, Moses; Yeu’l, Efrain; Heimann, Shmuel; Levy, Rachel; Friedman, G.; Zakay‐Rones, Zichria

doi:10.1016/s0264-410x(02)00481-4

Cited by 55 publications

(32 citation statements)

References 38 publications

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“…The use of an intranasal vaccine containing LTK63 with biovector as a mucosal adjuvant and a special delivery system shows promise in this respect, but whether the immune response in humans is adequate to prevent or ameliorate influenza virus infection has not been demonstrated, and further studies are required to answer this question. Overall, both intranasal and intramuscular vaccines were easy to administer and well tolerated, although the incidence of transient local pain and the use of analgesics or antipyretics were greater after intramuscular vaccination than after intranasal vaccination, which is consistent with previous findings (13,23). The safety of the intranasal vaccines containing the LTK63 enterotoxin mutant could not be evaluated effectively with the small numbers of subjects enrolled in this study.…”

Section: Discussionsupporting

confidence: 72%

Phase I Evaluation of Intranasal Trivalent Inactivated Influenza Vaccine with Nontoxigenic Escherichia coli Enterotoxin and Novel Biovector as Mucosal Adjuvants, Using Adult Volunteers

Stephenson

Zambon²,

Rudin³

et al. 2006

J Virol

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Trivalent influenza virus A/Duck/Singapore (H5N3), A/Panama (H3N2), and B/Guandong vaccine preparations were used in a randomized, controlled, dose-ranging phase I study. The vaccines were prepared from highly purified hemagglutinin and neuraminidase from influenza viruses propagated in embryonated chicken eggs and inactivated with formaldehyde. We assigned 100 participants to six vaccine groups, as follows. Three intranasally vaccinated groups received 7.5-g doses of hemagglutinin from each virus strain with either 3, 10, or 30 g of heat-labile Escherichia coli enterotoxin (LTK63) and 990 g of a supramolecular biovector; one intranasally vaccinated group was given 7.5-g doses of hemagglutinin with 30 g of

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Section: Discussionsupporting

confidence: 72%

Phase I Evaluation of Intranasal Trivalent Inactivated Influenza Vaccine with Nontoxigenic Escherichia coli Enterotoxin and Novel Biovector as Mucosal Adjuvants, Using Adult Volunteers

Stephenson

Zambon²,

Rudin³

et al. 2006

J Virol

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“…Thus, the local immune response is important for protection against novel strains and can stop the virus at its point of entry 22 and prevent transmission between individuals. In contrast, conventional parenterally injected vaccines induce a poor IgA response and therefore are unable to prevent the initial replication in the airways 18 , 23 , 24 , 25 and have shown reduced efficacy against drifted viruses 26 …”

Section: Introductionmentioning

confidence: 99%

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Svindland

Jul-Larsen

Pathirana

et al. 2011

Influenza Resp Viruses

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Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750‐2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose‐sparing strategies and an efficient mass‐vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose‐sparing potential of a chitosan‐adjuvanted intranasal H5N1 (RG‐14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)‐adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non‐adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG‐14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan‐adjuvanted SU vaccine induced an immune response superior to that of the non‐adjuvanted SU vaccine. Compared with the non‐adjuvanted SU group, the chitosan‐adjuvanted SU vaccine elicited higher numbers of influenza‐specific antibody‐secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T‐helper 1/T‐helper 2 cytokine response in the chitosan‐adjuvanted SU groups, and these groups had an increased percentage of virus‐specific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non‐adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan‐adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T‐helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFγ+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross‐clade serum reactivity, improved B‐ and T‐cell responses and dose‐sparing potential of chitosan show that a chitosan‐adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.

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“…Among these methods, intranasal administration, in which aerosolized vaccines are delivered through nose cavities, has drawn the attention of researchers as one of the most effective means for controlling diseases resulting from viral infection, especially in response to the increased demand for mass vaccination at relatively low cost compared to typical injection methods. In addition, intranasal vaccines have been shown to be significantly more effective than injection ones in inducing a mucosal immune response in response to influenza virus, as the portal of the virus entry is the mucosa layer that lines the respiratory tracts exposed to the external environment (Muszkat et al, 2003). Since several problems have been reported in using weakened live virus vaccine against influenza, including side effects in immune-compromised patients and the potential for reversion to pathogenic strains, many studies have suggested that intranasal delivery of inactivated influenza virus vaccine is a logical alternative (Smith et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Aerosol Particle Size Distribution and Genetic Characteristics of Aerosolized Influenza A H1N1 Virus Vaccine Particles

Lee

Kim

Lee

et al. 2011

Aerosol Air Qual. Res.

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Influenza has increasingly become a global issue that threatens human lives worldwide. While an aerosol-type influenza vaccine has been licensed for the treatment of seasonal influenza via intranasal administration, the physical and genetic characteristics of aerosols containing vaccine particles have not yet been reported in either a native or artificial environment. In this study, we aerosolized a conventional vaccine solution containing inactivated split influenza particles and measured the size distribution of the aerosol particles after nebulization. We also tested a novel method for detecting a minimal amount of the viral particles in the aerosols by amplifying the viral genomic RNAs in the vaccine solution via reverse transcription-PCR. In the results, we found via TEM that the morphology of the viral particles in the vaccine solution was not significantly deteriorated by the inactivation process. The aerosolized vaccine particles exhibited a mode diameter of 130 nm. In addition, the viral RNAs were successfully amplified from the inactivated split virus vaccine solution even after the nebulization process. Taken together, the current experimental results provide basic information regarding the general characteristics of the inactivated influenza viral particles in the vaccine, including genetic properties, and may contribute to the effective use of the vaccine solution in medical protocols.

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Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine

Cited by 55 publications

References 38 publications

Phase I Evaluation of Intranasal Trivalent Inactivated Influenza Vaccine with Nontoxigenic Escherichia coli Enterotoxin and Novel Biovector as Mucosal Adjuvants, Using Adult Volunteers

Phase I Evaluation of Intranasal Trivalent Inactivated Influenza Vaccine with Nontoxigenic Escherichia coli Enterotoxin and Novel Biovector as Mucosal Adjuvants, Using Adult Volunteers

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Aerosol Particle Size Distribution and Genetic Characteristics of Aerosolized Influenza A H1N1 Virus Vaccine Particles

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