Reply: Letter to the Editor, Cochrane Rearranged

Beyer, Walter; McElhaney, Janet E.; Smith, Derek J.; Monto, Arnold S.; Nguyen-Van-Tam, Jonathan S.; Osterhaus, Albert D. M. E.

doi:10.1016/j.vaccine.2014.05.045

Cited by 3 publications

(2 citation statements)

References 7 publications

(6 reference statements)

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“…Furthermore, a Cochrane review ( 21 ) questioning the effectiveness of influenza vaccine in older adults has been challenged on the basis of over-stratification of the data and loss of statistical power, and lack of separation of data from good vs. poor match vaccine to the circulating strains of influenza virus, and years with low vs. high levels of circulation of influenza. When these factors were taken into consideration, a re-analysis of the same studies included in the Cochrane review, provided estimates of vaccine effectiveness of 30% in older adults, consistent with the existing literature ( 22 , 23 ). Given that influenza vaccination remains a cost-saving medical intervention in older adults in spite of the well-recognized decline in vaccine effectiveness in older adults, recent advances in vaccine technology offer an unprecedented opportunity to improve influenza vaccines for this population.…”

Section: Burden Of Influenza Immune Senescence and Loss Of Vaccine mentioning

confidence: 55%

T-Cell Immunity to Influenza in Older Adults: A Pathophysiological Framework for Development of More Effective Vaccines

et al. 2016

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One of the most profound public health consequences of immune senescence is reflected in an increased susceptibility to influenza and other acute respiratory illnesses, as well as a loss of influenza vaccine effectiveness in older people. Common medical conditions and mental and psychosocial health issues as well as degree of frailty and functional dependence accelerate changes associated with immune senescence. All contribute to the increased risk for complications of influenza infection, including pneumonias, heart diseases, and strokes that lead to hospitalization, disability, and death in the over 65 population. Changes in mucosal barrier mechanisms and both innate and adaptive immune functions converge in the reduced response to influenza infection, and lead to a loss of antibody-mediated protection against influenza with age. The interactions of immune senescence and reduced adaptive immune responses, persistent cytomegalovirus infection, inflammaging (chronic elevation of inflammatory cytokines), and dysregulated cytokine production, pose major challenges to the development of vaccines designed to improve T-cell-mediated immunity. In older adults, the goal of vaccination is more realistically targeted to providing clinical protection against disease rather than to inducing sterilizing immunity to infection. Standard assays of antibody titers correlate with protection against influenza illness but do not detect important changes in cellular immune mechanisms that correlate with vaccine-mediated protection against influenza in older people. This article will discuss: (i) the burden of influenza in older adults and how this relates to changes in T-cell function, (ii) age-related changes in different T-cell subsets and immunologic targets for improved influenza vaccine efficacy in older, and (iii) the development of correlates of clinical protection against influenza disease to expedite the process of new vaccine development for the 65 and older population. Ultimately, these efforts will address the public health need for improved protection against influenza in older adults and “vaccine preventable disability.”

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Section: Burden Of Influenza Immune Senescence and Loss Of Vaccine mentioning

confidence: 55%

T-Cell Immunity to Influenza in Older Adults: A Pathophysiological Framework for Development of More Effective Vaccines

et al. 2016

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“…Seasonal influenza has a significant annual global impact accounting for an estimated 1 billion illnesses and 250,000-500,000 deaths 1 with an estimated economic cost of $87.1 billion in the US alone 2 . The unpredictable risk of sporadic outbreaks of human infections with avian influenza (H5N1) could trigger a new pandemic if the virus acquires the ability to transmit from person to person 3 .…”

Section: Introductionmentioning

confidence: 99%

A phase IIb study to determine the safety and efficacy of candidate INfluenza Vaccine MVA-NP+M1 in combination with licensed InaCTivated inflUenza vaccine in adultS aged 65 years and above (INVICTUS): a study protocol

et al. 2019

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Seasonal influenza has a significant annual global impact. Current influenza vaccines work by inducing strain-specific antibodies against the highly polymorphic surface proteins of the influenza virus and need to be redesigned every year, increasing their cost and limiting availability. There is a demand for a more efficacious vaccine, particularly in older adults in which the current vaccines show poor efficacy. The aim is to investigate a novel vaccine, MVA-NP+M1, which targets T cell responses to the nucleoprotein and matrix 1 core proteins of the influenza virus A, which are highly conserved, and therefore may provide long protection against a broad range of influenza strains. INVICTUS is a phase IIb study to determine the safety and efficacy of candidate INfluenza Vaccine MVA-NP+M1 in combination with licensed InaCTivated inflUenza vaccine in adultS aged 65 years and above is a randomised, participant-blinded, placebo-controlled, multi-centre phase IIb efficacy study planned for 2030 volunteers aged 65 and over, in primary care. The primary objective is to assess the efficacy of MVA-NP+M1 co-administered with licensed inactivated quadrivalent influenza vaccine in adults ≥65 years. Participants complete daily diaries to record solicited and unsolicited events in the first four weeks post vaccination, and influenza-like illness (ILI) symptoms and severity throughout the influenza season. We hypothesise an improvement in the primary outcome, a reduction in the average number of days spent with moderate or severe influenza-like illness during periods of influenza circulation, in the group administered with MVA-NP+M1, compared to those in the control group. Registration: ClinicalTrials.gov identifier NCT03300362. Protocol version: INVICTUS Protocol v3.0, 08 June06 2018.

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