Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects

Treanor, John J.; Nolan, Carrie; O'Brien, Diane; Burt, David S.; Lowell, George H.; Linden, Janine; Fries, Louis

doi:10.1016/j.vaccine.2005.07.088

Cited by 64 publications

(29 citation statements)

References 26 publications

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“…We identified 60 eligible articles published between 1987 and 2006 describing inactivated seasonal influenza vaccine immunogenicity studies conducted in the United States, Canada, Europe, Israel, and Russia 10 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 . We included 129 independent study arms of which 119 reported data on response to A/H1N1, 109 on influenza B, and 108 on A/H3N2 vaccine strains (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Quantitative review of antibody response to inactivated seasonal influenza vaccines

Seidman

Richard

Viboud

et al. 2011

Influenza Resp Viruses

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Please cite this paper as: Seidman et al. (2012) Quantitative review of antibody response to inactivated seasonal influenza vaccines. Influenza and Other Respiratory Viruses 6(1), 52–62. Background Seasonal influenza epidemics are associated with significant morbidity and mortality each year, particularly amongst young children and the elderly. Seasonal influenza vaccines have been available for decades, yet influenza remains a major public health threat in the US, sparking interest in studies evaluating the effectiveness of vaccination. Objectives We sought to identify determinants of serological responses to inactivated seasonal influenza vaccines including number of doses, adjuvant, and subject characteristics. Methods We reviewed 60 articles published between 1987 and 2006. We used weighted multiple logistic regression and random‐effects models to evaluate how seroconversion and seroprotection rates varied with host and vaccine factors. Results Both children and seniors tended to have poorer immune responses compared to adults whereas use of adjuvant and a second vaccine dose tended to improve immune response. Pre‐vaccination serological status had a large impact on the immune response to vaccination. We found substantial heterogeneity among studies, even with similar population settings and vaccination regimen. Conclusions Future studies should stratify their results by pre‐vaccination serological status in an effort to produce more precise summary estimates of vaccine response.

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Section: Resultsmentioning

confidence: 99%

Quantitative review of antibody response to inactivated seasonal influenza vaccines

Seidman

Richard

Viboud

et al. 2011

Influenza Resp Viruses

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“…In this context, we examined the immunomodulatory potential of Protollin, a mucosal vaccine adjuvant composed of TLR2 and TLR4 ligands, in a murine model of experimental allergic asthma (11). Protollin was determined to be safe and well-tolerated up to a dose of 1.5 mg LPS when administered via the intranasal route in phase I (12) and II (13) human clinical trials, and has been tested as an intranasal vaccine adjuvant in animal models of influenza (14), respiratory syncytial virus (15), severe acute respiratory syndrome (16), plague (Yersinia pestis) (17), and measles (18) infection, as well as in models of Alzheimer's disease (19). Protollin consists of LPS molecules (TLR4 ligand) from Shigella flexneri, a Gram-negative bacterium, noncovalently incorporated in nanomolecular vesicles formed by proteosomes, consisting of purified hydrophobic outer-membrane proteins from Neisseria meningitidis (shown to signal via a TLR2/1 heterodimer complex) (20,21).…”

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confidence: 99%

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Shalaby

Nakada

et al. 2012

The Journal of Immunology

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Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2−/−, or Tlr4−/− BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges. Nasal application of Protollin or Protollin admixed with BPEx was sufficient to inhibit allergic lower airway disease with minimal collateral lung inflammation. Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4+Foxp3+ and CD4+Foxp3− T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs. Adoptive transfer of cervical LN CD4+ICOS+, but not CD4+ICOS−, cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia. Thus, our data indicate that expansion of resident ICOS-expressing CD4+ T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.

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“…In that regard, Protollin (proteosomes-LPS) can activate antigen-presenting cells via both TLR2 and TLR4, inducing a more polarized Th1 response (8). More importantly, proteosomes have been shown to be potent intranasal adjuvants inducing proinflammatory cytokines (IFN-␥ and IL-5) in mouse splenocytes (25) and having a favorable safety profile in preclinical studies as well as in humans (17,29,38,46). An i.n.…”

Section: Discussionmentioning

confidence: 99%

Effects of Different Adjuvants in the Context of Intramuscular and Intranasal Routes on Humoral and Cellular Immune Responses Induced by Detergent-Split A/H3N2 Influenza Vaccines in Mice

Baz

Samant

Zekki

et al. 2012

Clin Vaccine Immunol

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Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects

Cited by 64 publications

References 26 publications

Quantitative review of antibody response to inactivated seasonal influenza vaccines

Quantitative review of antibody response to inactivated seasonal influenza vaccines

ICOS-Expressing CD4 T Cells Induced via TLR4 in the Nasal Mucosa Are Capable of Inhibiting Experimental Allergic Asthma

Effects of Different Adjuvants in the Context of Intramuscular and Intranasal Routes on Humoral and Cellular Immune Responses Induced by Detergent-Split A/H3N2 Influenza Vaccines in Mice

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