A Rapid Immune Response to 2009 Influenza A(H1N1) Vaccines in Adults: A Randomized, Double‐Blind, Controlled Trial

ABSTRACT We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.

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Adjuvant Effect of Orally Applied Preparations Containing Non-Digestible Polysaccharides on Influenza Vaccination in Healthy Seniors: A Double-Blind, Randomised, Controlled Pilot Trial

Nutrients ◽

10.3390/nu13082683 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2683

Author(s):

Christiane Laue ◽

Yala Stevens ◽

Monique van Erp ◽

Ekaterina Papazova ◽

Edlyn Soeth ◽

...

Keyword(s):

Immune Response ◽

Influenza A ◽

Pilot Trial ◽

Haemagglutination Inhibition ◽

Fisher Exact Test ◽

Adjuvant Effect ◽

Seroprotection Rate ◽

Double Blind ◽

Influenza A H1n1 ◽

Randomised Controlled

Senior individuals can suffer from immunosenescence and novel strategies to bolster the immune response could contribute to healthy ageing. In this double-blind, randomised, controlled pilot trial, we investigated the ability of non-digestible polysaccharide (NPS) preparations to enhance the immune response in a human vaccination model. In total, 239 subjects (aged 50–79 years) were randomised to consume one of five different NPS (yeast β-glucan (YBG), shiitake β-glucan (SBG), oat β-glucan (OBG), arabinoxylan (AX), bacterial exopolysaccharide (EPS)) or control (CTRL) product daily for five weeks. After two weeks of intervention, subjects were vaccinated with seasonal influenza vaccine. The post-vaccination increases in haemagglutination inhibition antibody titres and seroprotection rate against the influenza strains were non-significantly enhanced in the NPS intervention groups compared to CTRL. Specifically, a trend towards a higher mean log2 fold increase was observed in the AX group (uncorrected p = 0.074) combined with a trend for an increased seroprotection rate, AX group (48.7%) compared to CTRL (25.6%) (uncorrected p = 0.057), for the influenza A H1N1 strain. Subjects consuming AX also had a reduced incidence of common colds compared to CTRL (1 vs. 8; p = 0.029 in Fisher exact test). No adverse effects of NPS consumption were reported. The findings of this pilot study warrant further research to study AX as an oral adjuvant to support vaccine efficacy.

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Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1725 ◽

2020 ◽

Author(s):

Alison Han ◽

Lindsay Czajkowski ◽

Luz Angela Rosas ◽

Adriana Cervantes-Medina ◽

Yongli Xiao ◽

...

Keyword(s):

Influenza A ◽

Controlled Trial ◽

Influenza Infection ◽

Area Under The Curve ◽

Surface Protein ◽

Healthy Human ◽

Double Blind ◽

Duration Of Symptoms ◽

Influenza A H1n1 ◽

Clinically Significant

Abstract Background It is imperative to identify new targets for improved vaccines and therapeutics against influenza and one such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. Methods We conducted a randomized, double-blind, Phase II placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. A single 50mg/kg dose of CR6261 was infused 24 hours after challenge and the primary efficacy outcome was area under the curve of viral RNA detection over time. Results Ninety-one healthy volunteers were randomized and underwent influenza challenge; 49 received CR6261 and 42 placebo. CR6261 had no statistically significant effect on AUC (AUC 48.56 log (copies/mL) x days, IQR 202 vs. AUC 25.53 log (copies/mL) x days, IQR 155), P=0.315), and no clinically significant effect on influenza disease measures including number of symptoms, duration of symptoms, or FLU-PRO scores. Preexisting anti-NA antibody titers were most predictive of reduced influenza disease. CR6261 reached a mean peak serum concentration of 1x10 6 ng/ml 15 minutes after infusion, and a mean peak of 5.97x10 2 ng/ml in the nasal mucosa 2-3 days after infusion. Conclusions The results of this study suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may be limited in efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multi-faceted strategy rather than as a standalone therapeutic.

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1522. Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1703 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S763-S763

Author(s):

Alison Han ◽

Lindsay Czajkowski ◽

Luz Angela Rosas ◽

Adriana Cervantes-Medina ◽

Yongli Xiao ◽

...

Keyword(s):

Pharmaceutical Company ◽

Influenza A ◽

Controlled Trial ◽

Influenza Infection ◽

Healthy Human ◽

Double Blind ◽

Duration Of Symptoms ◽

Viral Shedding ◽

Influenza A H1n1 ◽

Significant Difference

Abstract Background Influenza virus infections cause significant morbidity and mortality during yearly seasonal epidemics and during sporadic pandemics. It is imperative to identify new targets for vaccines and therapeutics. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. Methods We conducted a randomized, double-blind, Phase II placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. CR6261 was infused 24 hours after challenge with H1N1pdm09 and the primary efficacy outcome was area under the curve (AUC) of viral shedding. Results Between March 2015-May 2018, 104 healthy volunteers were enrolled and randomized with 91 undergoing influenza challenge, of which 49 participants (54%) received treatment with CR6261 and 42 participants (46%) received placebo. A mean of 1x106 ng/mL of serum CR6261 was detected by 24 hours after infusion. Nasal CR6261 levels reached a peak mean of 5.97x102 ng/ml 2 days after infusion. There was no statistically significant difference in the primary outcome measure between the CR6261 group and placebo (median AUC 48.56 and 25.53 respectively, P=0.31). The severity of illness was compared between the two groups, and no significant difference was observed in number of symptoms, duration of symptoms, or FLU-PRO scores. Conclusion CR6261 had no statistically significant effect on AUC of viral shedding, and no clinically significant effect on overall influenza disease. Preexisting anti-neuraminidase (NA) antibody titers were most predictive of reduced influenza disease. Nasal CR6261 levels were much lower compared to serum, which may be a factor in the limited effect of CR6261 on this upper respiratory infection. These results suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may have limited efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multi-faceted strategy rather than as a standalone therapeutic or vaccine strategy. Funding This study was funded in part by the intramural program of NIAID, NIH, by the NCI Contract No. 75N910D00024, Task Order No. 75N91019F00130, and through a CRADA with Janssen Infectious Diseases and Vaccines. Disclosures Amy Lwin, RN, BSN, Janssen Pharmaceutical Company of J&J (Employee) Jerald Sadoff, MD, Janssen Pharmaceutical Company of J&J (Employee)

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Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: a multicentre, double-blind, randomised, placebo-controlled trial

The Lancet ◽

10.1016/s0140-6736(09)62003-1 ◽

2010 ◽

Vol 375 (9708) ◽

pp. 56-66 ◽

Cited By ~ 178

Author(s):

Xiao-Feng Liang ◽

Hua-Qing Wang ◽

Jun-Zhi Wang ◽

Han-Hua Fang ◽

Jiang Wu ◽

...

Keyword(s):

Pandemic Influenza ◽

Influenza A ◽

Controlled Trial ◽

Double Blind ◽

Influenza A H1n1

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Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial

Nutrients ◽

10.3390/nu14010228 ◽

2022 ◽

Vol 14 (1) ◽

pp. 228

Author(s):

Anxo Fernández-Ferreiro ◽

Francisco J. Formigo-Couceiro ◽

Roi Veiga-Gutierrez ◽

Jose A. Maldonado-Lobón ◽

Ana M. Hermida-Cao ◽

...

Keyword(s):

Immune Response ◽

Controlled Trial ◽

Severe Disease ◽

Nursing Home Residents ◽

Vaccination Schedule ◽

Elderly Subjects ◽

Double Blind ◽

Iga Antibody ◽

Specific Igg ◽

Antibody Levels

Elderly people are particularly vulnerable to COVID-19, with a high risk of developing severe disease and a reduced immune response to the COVID-19 vaccine. A randomized, placebo-controlled, double-blind trial to assess the effect of the consumption of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on the immune response generated by the COVID-19 vaccine in an elderly population was performed. Two hundred nursing home residents >60 yrs that had not COVID-19 were randomized to receive L. coryniformis K8 or a placebo daily for 3 months. All volunteers received a complete vaccination schedule of a mRNA vaccine, starting the intervention ten days after the first dose. Specific IgG and IgA antibody levels were analyzed 56 days after the end of the immunization process. No differences between the groups were observed in the antibody levels. During the intervention, 19 subjects had COVID-19 (11 receiving K8 vs. 8 receiving placebo, p = 0.457). Subgroup analysis in these patients showed that levels of IgG were significantly higher in those receiving K8 compared to placebo (p = 0.038). Among subjects >85 yrs that did not get COVID-19, administration of K8 tended to increase the IgA levels (p = 0.082). The administration of K8 may enhance the specific immune response against COVID-19 and may improve the COVID-19 vaccine-specific responses in elderly populations.

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