13 research outputs found
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
Serum HAI antibody responses at Day 39±3 following first nasal administration of trivalent Proteosome-influenza vaccine.
<p>Serum HAI antibody responses at Day 39±3 following first nasal administration of trivalent Proteosome-influenza vaccine.</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
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
CONSORT Flowchart for Study 2 (Study Protocol 13005)
<p>CONSORT Flowchart for Study 2 (Study Protocol 13005)</p
Percentage vaccine efficacy by treatment group
<p>Percentage vaccine efficacy by treatment group</p
Correlation of serum IgG (HAI) and mucosal sIgA levels at Day 39±3 and rates of any influenza symptoms and seroconversion following viral challenge
<p>Correlation of serum IgG (HAI) and mucosal sIgA levels at Day 39±3 and rates of any influenza symptoms and seroconversion following viral challenge</p
Nasal virus-specific secretory IgA responses at Day 39±3 after first nasal administration of trivalent Proteosome influenza vaccine.
<p>Nasal virus-specific secretory IgA responses at Day 39±3 after first nasal administration of trivalent Proteosome influenza vaccine.</p