Spontaneous ciliary activity during development.

<p>A: Three representative waveforms of spontaneous ciliary motion measured from ciliated cells near the pharyngeal opening using a photodiode-based displacement measurement system. The responses were obtained from three different cells at P1. B: The power spectra of ciliary motion of the waveforms shown in Panel A. C: Means and SD of beat frequencies during different stages of development. The means are based on measurements made from 12 cells from three animals for each age group.</p

Ciliary motion measured from adult gerbils.

<p>A: Three representative waveforms of spontaneous ciliary motion measured from three different ciliated cells near the pharyngeal opening using a photodiode-based displacement measurement system. Different patterns of responses with different frequencies and magnitudes were observed. B: The power spectra of cilia motion. The spectra represent five averages (in the frequency domain) of spontaneous ciliary response acquired in a four-second window in each trial. C: Means and SDs of ciliary beat frequency. The responses were measured from 15 ciliated cells in the cartilage and osseous portion of the ET from five animals. For comparison, ciliary motion was also measured from 12 ciliated cells in the airway of three adult gerbils. No statistical difference (p>0.05) of the beat frequency was found among ciliated cells in the different regions.</p

SEM pictures of the mucosal epithelium acquired from two areas near the pharyngeal and tympanic openings in the ET during development.

<p>Bars: 30 µm.</p

Longitudinal section of the TB of a 30-day-old gerbil stained with hematoxylin and eosin.

<p>The length of the Eustachian tube measured between the tympanic and pharyngeal ends in adult gerbil is ∼0.8 mm. Bar: 50 µm.</p

SEM pictures of ciliated epithelium near the pharyngeal opening (A) and tympanic opening (B) of the ET from a P30 gerbil.

<p>Note that the density of ciliated cells near the pharyngeal opening is significantly greater than that near the tympanic opening. Black arrows indicate mucus drops. Bar: 15 µm for panels A and B. C: High magnification picture of ciliated cells and goblet cells in the area near the pharyngeal opening. G stands for goblet cells. D: High magnification picture of ciliated cells and squamous cells in the area near the tympanic opening. Note that there was absorption of cilia (marked by black arrows). Bar: 5 µm for C and D.</p

Morphological development of the ET.

<p>A: Longitudinal sections prepared from neonatal gerbils at P1, P8, P12, P18, and P30. B: Means and SDs of length of the ET (measured between the pharyngeal opening and the tympanic opening). The measurements were made from five temporal bone preparations from five animals for each age group.</p

An Intranasal Proteosome-Adjuvanted Trivalent Influenza Vaccine Is Safe, Immunogenic & Efficacious in the Human Viral Influenza Challenge Model. Serum IgG & Mucosal IgA Are Important Correlates of Protection against Illness Associated with Infection

<div><p>Introduction</p><p>A Proteosome-adjuvanted trivalent inactivated influenza vaccine (P-TIV) administered intra-nasally was shown to be safe, well tolerated and immunogenic in both systemic and mucosal compartments, and effective at preventing illness associated with evidence of influenza infection.</p><p>Methods</p><p>In two separate studies using the human viral challenge model, subjects were selected to be immunologically naive to A/Panama/2007/1999 (H3N2) virus and then dosed via nasal spray with one of three regimens of P-TIV or placebo. One or two doses, 15 μg or 30 μg, were given either once only or twice 14 days apart (1 x 30 μg, 2 x 30 μg, 2 x 15 μg) and subjects were challenged with A/Panama/2007/1999 (H3N2) virus. Immune responses to the vaccine antigens were measured by haemagglutination inhibition assay (HAI) and nasal wash secretory IgA (sIgA) antibodies.</p><p>Results</p><p>Vaccine reactogenicity was mild, predictable and generally consistent with earlier Phase I studies with this vaccine. Seroconversion to A/Panama/2007/1999 (H3N2), following vaccination but prior to challenge, occurred in 57% to 77% of subjects in active dosing groups and 2% of placebo subjects. The greatest relative rise in sIgA, following vaccination but prior to challenge, was observed in groups that received 2 doses.</p><p>Conclusion</p><p>Intranasal vaccination significantly protected against influenza (as defined by influenza symptoms combined with A/Panama seroconversion) following challenge with A/Panama/2007/1999 (H3N2). When data were pooled from both studies, efficacy ranged from 58% to 82% in active dosing groups for any influenza symptoms with seroconversion, 67% to 85% for systemic or lower respiratory illness and seroconversion, and 65% to 100% for febrile illness and seroconversion. The two dose regimen was found to be superior to the single dose regimen. In this study, protection against illness associated with evidence of influenza infection (evidence determined by seroconversion) following challenge with virus, significantly correlated with pre-challenge HAI titres (p = 0.0003) and mucosal sIgA (p≤0.0001) individually, and HAI (p = 0.028) and sIgA (p = 0.0014) together. HAI and sIgA levels were inversely related to rates of illness.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT02522754" target="_blank">NCT02522754</a></p></div

Overall summary of frequency of adverse events by treatment group.

<p>Overall summary of frequency of adverse events by treatment group.</p

Proportion of subjects in each treatment group meeting specified post-challenge endpoints and apparent efficacy versus Placebo (pooled data).

<p>Proportion of subjects in each treatment group meeting specified post-challenge endpoints and apparent efficacy versus Placebo (pooled data).</p

Physician Examination Reactogenicity in the 7 Days Following Dose 1 and Dose 2 of Vaccine Pooled Data.

<p>Physician Examination Reactogenicity in the 7 Days Following Dose 1 and Dose 2 of Vaccine Pooled Data.</p