Humoral and Cell-Mediated Immune Responses to Monovalent 2009 Influenza A/H1N1 and Seasonal Trivalent Influenza Vaccines in High-Risk Children

The current pandemic has brought a renewed appreciation for the critical importance of vaccines for the promotion of both individual and public health. Influenza vaccines have been our primary tool for infection control to prevent seasonal epidemics and pandemics such as the 2009 H1N1 influenza A virus pandemic. Certain high-risk populations, including the elderly, people with obesity, and individuals with comorbidities such as type 2 diabetes mellitus, are more susceptible to increased disease severity and decreased vaccine efficacy. High-risk populations have unique microenvironments and immune responses that contribute to increased vulnerability for influenza infections. This review focuses on these differences as we investigate the variations in immune responses to influenza vaccination. In order to develop better influenza vaccines, it is critical to understand how to improve responses in our ever-growing high-risk populations.

Download Full-text

Intersection of Sex and Frailty in Humoral Immune Responses to Influenza Vaccine in Community-Dwelling Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.869 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 271-272

Author(s):

Janna Shapiro ◽

Helen Kuo ◽

Rosemary Morgan ◽

Huifen Li ◽

Sabra Klein ◽

...

Keyword(s):

Older Adults ◽

Immune Responses ◽

Influenza A ◽

Community Dwelling ◽

Influenza Vaccines ◽

Health Study ◽

Cardiovascular Health Study ◽

High Dose ◽

Humoral Immune ◽

Humoral Immune Responses

Abstract Older adults bear the highest burden of severe disease and complications associated with seasonal influenza, with annual vaccination serving as the best option for protection. Variability in vaccine efficacy exists, yet the host factors that affect immune responses to inactivated influenza vaccines (IIV) are incompletely understood. We hypothesized that sex and frailty interact to affect vaccine-induced humoral responses among older adults. To test this hypothesis, community-dwelling adults above 75 years of age were recruited yearly, assessed for frailty (as defined by the Cardiovascular Health Study criteria), and vaccinated with the high-dose trivalent IIV. Humoral immune responses were evaluated via hemagglutination inhibition titers. The study began during the 2014-2015 influenza season, with yearly cohorts ranging from 76-163 individuals. A total of 617 vaccinations were delivered from 2014-2019. In preliminary analyses, the outcome of interest was seroconversion, defined as ≥ 4-fold rise in titers. Crude odds ratios suggest that females are more likely to seroconvert to influenza A strains (H1N1: OR = 1.39, (0.98-1.96) ; H3N2: 1.17 (0.85 – 1.62)), while males are more likely to seroconvert to the B strain (OR = 0.85 (0.60 – 1.22)). Furthermore, this sex difference was modified by frailty – for example, the odds of seroconversion to H1N1 were 65% higher for females than males among those who were nonfrail, and only 30% higher among females who were frail. Together, these results suggest that sex and frailty interact to impact immune responses to influenza vaccines. These findings may be leveraged to better protect vulnerable populations.

Download Full-text

Effectiveness of Influenza Vaccines in the HIVE household cohort over 8 years: is there evidence of indirect protection?

10.1101/2021.02.16.21251827 ◽

2021 ◽

Author(s):

Ryan E. Malosh ◽

Joshua G. Petrie ◽

Amy Callear ◽

Rachel Truscon ◽

Emileigh Johnson ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

Vaccine Coverage ◽

Influenza Virus Infection ◽

Influenza Vaccines ◽

Mixed Effect ◽

Vaccination Programs ◽

Vaccine Recommendations ◽

Influenza A H1n1 ◽

Low Coverage

AbstractBackgroundThe evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (i.e. indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort.MethodsUsing longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households.ResultsThe pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8); and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (−6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccine coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VET was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households.ConclusionInfluenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. While there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.

Download Full-text

Clinical and Immune Responses to Inactivated Influenza A(H1N1)pdm09 Vaccine in Children

The Pediatric Infectious Disease Journal ◽

10.1097/01.inf.0000456034.46241.ea ◽

2014 ◽

Vol 33 (11) ◽

pp. 1207

Author(s):

&NA;

Keyword(s):

Immune Responses ◽

Influenza A ◽

Influenza A H1n1

Download Full-text

Seasonal influenza vaccines induced high levels of neutralizing cross-reactive antibody responses against different genetic group influenza A(H1N1)pdm09 viruses

Vaccine ◽

10.1016/j.vaccine.2019.03.078 ◽

2019 ◽

Vol 37 (20) ◽

pp. 2731-2740 ◽

Cited By ~ 1

Author(s):

Anu Haveri ◽

Niina Ikonen ◽

Anu Kantele ◽

Veli-Jukka Anttila ◽

Eeva Ruotsalainen ◽

...

Keyword(s):

Influenza A ◽

Seasonal Influenza ◽

Antibody Responses ◽

Genetic Group ◽

Influenza Vaccines ◽

Influenza A H1n1 ◽

Reactive Antibody

Download Full-text

Administration of the Adjuvanted pH1N1 Vaccine in Egg-allergic Children at High Risk for Influenza A/H1N1 Disease

Can J Public Health ◽

10.1007/bf03404895 ◽

2011 ◽

Vol 102 (3) ◽

pp. 196-199 ◽

Cited By ~ 7

Author(s):

Jane E. SchulerCHEO ◽

W. James King ◽

Natalie L. Dayneka ◽

Lynn Rastelli ◽

Evelyn Marquis ◽

...

Keyword(s):

High Risk ◽

Influenza A ◽

Influenza A H1n1

Download Full-text

Long-Lasting Mucosal and Systemic Immunity against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice

Vaccines ◽

10.3390/vaccines7030064 ◽

2019 ◽

Vol 7 (3) ◽

pp. 64 ◽

Cited By ~ 2

Author(s):

Jorma Hinkula ◽

Sanna Nyström ◽

Claudia Devito ◽

Andreas Bråve ◽

Steven E. Applequist

Keyword(s):

Immune Responses ◽

Influenza A Virus ◽

Influenza A ◽

Influenza Infection ◽

Inbred Mouse ◽

Herd Immunity ◽

Serum Antibody ◽

Mouse Strains ◽

Virus Challenge ◽

Influenza A H1n1

Background: Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods: Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results: WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4+ and CD8+ T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions: These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

Download Full-text