Immunogenicity of AS03-adjuvanted and non-adjuvanted trivalent inactivated influenza vaccines in elderly adults: A Phase 3, randomized trial and <i>post-hoc</i> correlate of protection analysis

Ruíz-Palacios, Guillermo M.; Leroux‐Roels, Geert; Beran, Jiřı́; Devaster, Jeanne-Marie; Esen, Meral; Launay, Odile; McElhaney, Janet E.; Essen, G A van; Benoît, André; Claeys, Carine; Dewé, Walthère; Durand, Christelle; Duval, Xavier; Falsey, Ann R.; Feldman, Gregory; Galtier, Florence; Gervais, Pierre; Hwang, Shinn‐Jang; McNeil, Shelly; Richardus, Jan Hendrik; Trofa, Andrew F.; Oostvogels, Lidia

doi:10.1080/21645515.2016.1219809

Cited by 7 publications

(8 citation statements)

References 28 publications

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“…However, even though the primary endpoint was missed, clear benefits were observed in secondary and exploratory readouts. Specifically, efficacy against A/H3N2 influenza infection as well as all-cause mortality and pneumonia was demonstrated in a post hoc analysis 45 , 46 . Hence, although the Influence65 study did not support licensure, the study did highlight the potential benefits of an adjuvanted influenza vaccine for older adults, even during seasons with partially mismatched influenza strains.…”

Section: Introductionmentioning

confidence: 99%

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

et al. 2021

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Emulsion adjuvants such as MF59 and AS03 have been used for more than two decades as key components of licensed vaccines, with over 100 million doses administered to diverse populations in more than 30 countries. Substantial clinical experience of effectiveness and a well-established safety profile, along with the ease of manufacturing have established emulsion adjuvants as one of the leading platforms for the development of pandemic vaccines. Emulsion adjuvants allow for antigen dose sparing, more rapid immune responses, and enhanced quality and quantity of adaptive immune responses. The mechanisms of enhancement of immune responses are well defined and typically characterized by the creation of an “immunocompetent environment” at the site of injection, followed by the induction of strong and long-lasting germinal center responses in the draining lymph nodes. As a result, emulsion adjuvants induce distinct immunological responses, with a mixed Th1/Th2 T cell response, long-lived plasma cells, an expanded repertoire of memory B cells, and high titers of cross-neutralizing polyfunctional antibodies against viral variants. Because of these various properties, emulsion adjuvants were included in pandemic influenza vaccines deployed during the 2009 H1N1 influenza pandemic, are still included in seasonal influenza vaccines, and are currently at the forefront of the development of vaccines against emerging SARS-CoV-2 pandemic variants. Here, we comprehensively review emulsion adjuvants, discuss their mechanism of action, and highlight their profile as a benchmark for the development of additional vaccine adjuvants and as a valuable tool to allow further investigations of the general principles of human immunity.

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Section: Introductionmentioning

confidence: 99%

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

et al. 2021

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“…Three different bins were used to define the window for the second serum collection; 20% of samples were 3–4 months post-vaccination, 30% were 5–7 months post-vaccination, 40% were 8–10 months post-vaccination, and 10% were 11–12 months post-vaccination. The rationale for selecting more samples 5–10 months post-vaccination was based on publications indicating that protective HI titers were maintained up to 6 months before dropping to non-protective levels [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…Some studies have indicated the benefits of vaccination can extend into the following season [ 5 , 10 , 11 , 12 , 13 , 14 ] while another study indicated that such antibody levels drop below accepted protective levels within a year [ 15 ]. Measurements of HI titers 180 days post-vaccination suggest that a significant portion of vaccinated subjects retain protective titers up to this point [ 16 ], but it is known that a reduction in vaccine effectiveness occurs later in the season, or in between seasons [ 17 , 18 , 19 , 20 ]. This has implications for those travelling between the northern and southern hemispheres, military personal posted to different regions of the globe, and at risk people vaccinated early during a season when influenza virus infections emerge late in the season.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Birth Year, Age and Sex on Hemagglutination Inhibition Antibody Responses to Influenza Vaccination

et al. 2018

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The first exposure to influenza is thought to impact subsequent immune responses later in life. The consequences of this can be seen during influenza epidemics and pandemics with differences in morbidity and mortality for different birth cohorts. There is a need for better understanding of how vaccine responses are affected by early exposures to influenza viruses. In this analysis of hemagglutination inhibition (HI) antibody responses in two cohorts of military personnel we noticed differences related to age, sex, prior vaccination, deployment and birth year. These data suggest that HI antibody production, in response to influenza vaccination, is affected by these factors. The magnitude of this antibody response is associated with, among other factors, the influenza strain that circulated following birth.

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“…This approach is especially practical for important subgroups of the population, such as older adults living with frailty and/or chronic conditions, who are at an increased risk of influenza hospitalization [ 8 ] and severity of related outcomes [ 9 ], regardless of vaccination status [ 10 ]. That being said, few correlates have been validated in older adults, and those that have are based primarily on hemagglutination inhibition antibody responses [ 11 , 12 ], which do not provide appreciable cross-strain immunity within the subtypes of influenza. Immunological measures such as broadly neutralizing antibodies [ 13 ] and interferon gamma (IFNγ) producing T-cells [ 14 , 15 , 16 , 17 , 18 ] are cross-reactive within the subtypes of influenza A, which may provide protection in the years when there is a vaccine strain mismatch to circulating strain of influenza virus.…”

Section: Introductionmentioning

confidence: 99%

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults

et al. 2021

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Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-(n = 17) or B-LCII (n = 9) at 10–20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection.

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Immunogenicity of AS03-adjuvanted and non-adjuvanted trivalent inactivated influenza vaccines in elderly adults: A Phase 3, randomized trial and post-hoc correlate of protection analysis

Cited by 7 publications

References 28 publications

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

The Effects of Birth Year, Age and Sex on Hemagglutination Inhibition Antibody Responses to Influenza Vaccination

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults

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