B Cell and Antibody Response to Seasonal Influenza Vaccines in Younger and Older Adults

Background: Improved seasonal influenza vaccines for older adults are urgently needed, which can induce broadly cross-reactive antibodies and enhanced T-cell responses, particularly against A(H3N2) viruses, while avoiding egg-adaptive antigenic changes. Methods: We randomized 2654 clinically-stable, community-dwelling adults ≥65 years of age 1:1 to receive a single intramuscular dose of either Matrix-M-adjuvanted quadrivalent nanoparticle influenza vaccine (qNIV) or a licensed inactivated influenza vaccine (IIV4) in this randomized, observer-blinded, active-comparator controlled trial conducted during the 2019-2020 influenza season. The primary objectives were to demonstrate the non-inferior immunogenicity of qNIV relative to IIV4 against 4 vaccine-homologous strains, based on Day 28 hemagglutination-inhibiting (HAI) antibody responses, described as geometric mean titers and seroconversion rate difference between treatment groups, and to describe the safety of qNIV. Cell-mediated immune (CMI) responses were measured by intracellular cytokine analysis. Findings: qNIV demonstrated immunologic non-inferiority to IIV4 against 4 vaccine-homologous strains as assessed by egg-based HAI antibody responses. Corresponding wild-type HAI antibody responses by qNIV were significantly higher than IIV4 against all 4 vaccine-homologous strains (22-66% increased) and against 6 heterologous A(H3N2) strains (34-46% increased), representing multiple genetically and/or antigenically distinct clades/subclades (all p-values <0.001). qNIV induced 3·1- to 3·9- and 4·0- to 4·9-fold increases in various polyfunctional phenotypes of antigen-specific effector CD4+ T-cells against A(H3N2) and B/Victoria strains at Day 7 post-vaccination, respectively, while corresponding fold-rises induced by IIV4 at Day 7 were 1·3-1·4 and 1·7-2·0 representing a 126-189% improvement in CMI responses for qNIV (all p-values <0·001). Local reactogenicity, primarily mild to moderate and transient pain, was higher in the qNIV group. Interpretation: qNIV was well tolerated and produced a qualitatively and quantitatively enhanced humoral and cellular immune response in older adults. These enhancements may be critical to improving the effectiveness of currently licensed influenza vaccines.

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A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration

Human Vaccines & Immunotherapeutics ◽

10.4161/hv.28618 ◽

2014 ◽

Vol 10 (6) ◽

pp. 1701-1710 ◽

Cited By ~ 14

Author(s):

Giovanni Della Cioppa ◽

Uwe Nicolay ◽

Kelly Lindert ◽

Geert Leroux-Roels ◽

Frédéric Clement ◽

...

Keyword(s):

Older Adults ◽

Seasonal Influenza ◽

Influenza Vaccines ◽

Intramuscular Administration ◽

Dose Ranging

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Quantitative review of antibody response to inactivated seasonal influenza vaccines

Influenza and Other Respiratory Viruses ◽

10.1111/j.1750-2659.2011.00268.x ◽

2011 ◽

Vol 6 (1) ◽

pp. 52-62 ◽

Cited By ~ 32

Author(s):

Jessica C. Seidman ◽

Stephanie A. Richard ◽

Cécile Viboud ◽

Mark A. Miller

Keyword(s):

Antibody Response ◽

Seasonal Influenza ◽

Influenza Vaccines ◽

Quantitative Review

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Somatic hypermutations and isotype switches in the progeny of a single virgin B cell predominating the human antibody response to the capsular polysaccharide of Haemophilus influenzae type b

Immunology Letters ◽

10.1016/s0165-2478(97)87211-2 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 95

Author(s):

T Barington

Keyword(s):

Antibody Response ◽

Haemophilus Influenzae ◽

B Cell ◽

Capsular Polysaccharide ◽

Haemophilus Influenzae Type ◽

Human Antibody ◽

Haemophilus Influenzae Type B ◽

Type B

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Hide and seek: interplay between influenza viruses and B cells

International Immunology ◽

10.1093/intimm/dxaa028 ◽

2020 ◽

Vol 32 (9) ◽

pp. 605-611 ◽

Cited By ~ 2

Author(s):

Masayuki Kuraoka ◽

Yu Adachi ◽

Yoshimasa Takahashi

Keyword(s):

B Cells ◽

B Cell ◽

Surface Protein ◽

Influenza Viruses ◽

Influenza Vaccines ◽

Native Structure ◽

Humoral Immune ◽

Protective Antibodies ◽

Major Surface ◽

And Function

Abstract Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

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Willingness to Receive the COVID-19 and Seasonal Influenza Vaccines among the Saudi Population and Vaccine Uptake During the Initial Stage of the National Vaccination Campaign: A Cross-Sectional Survey

Vaccines ◽

10.3390/vaccines9070765 ◽

2021 ◽

Vol 9 (7) ◽

pp. 765

Author(s):

Amel Ahmed Fayed ◽

Abeer Salem Al Shahrani ◽

Leenah Tawfiq Almanea ◽

Nardeen Ibrahim Alsweed ◽

Layla Mohammed Almarzoug ◽

...

Keyword(s):

Saudi Arabia ◽

Perceived Risk ◽

Online Survey ◽

Seasonal Influenza ◽

Vaccination Campaign ◽

Vaccine Uptake ◽

Influenza Vaccines ◽

Vaccine Hesitancy ◽

Cross Sectional ◽

To Receive

This study aimed to assess the willingness to receive the coronavirus disease 2019 (COVID-19) and seasonal influenza vaccines and vaccine uptake during the early stage of the national vaccination campaign in Saudi Arabia. A cross-sectional online survey was conducted among adult Saudis between 20 January and 20 March 2021. The questionnaire addressed vaccine hesitancy, perceived risk, willingness, and vaccine uptake. Approximately 39% of the participants expressed vaccine hesitancy, and 29.8% and 24% felt highly vulnerable to contracting COVID-19 and seasonal influenza, respectively. The majority (59.5%) were willing to receive the COVID-19 vaccine, although only 31.7% were willing to receive the flu vaccine. Adjusted analysis showed that vaccine hesitancy (OR 0.34, 95% CI 0.27–0.43) and the perception of being at high risk (OR 2.78, 95% CI 1.68–4.60) independently affected the intention to be vaccinated. Vaccine hesitancy was similar among those who were willing to be vaccinated (29.8%) and those who had already been vaccinated (33.1%). The perceived risk was significantly higher among those who had been vaccinated (48.1%) than among those who were willing to be vaccinated but had not yet been vaccinated (29.1%). In conclusion, the acceptance of the COVID-19 vaccine in Saudi Arabia is high. Saudis who received the vaccine had a similar level of vaccine hesitancy and a higher level of perceived risk.

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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.

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