Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older

Dunkle, Lisa M.; Izikson, Ruvim; Patriarca, P.; Goldenthal, Karen L.; Muse, Derek; Callahan, Janice D.; Cox, Manon

doi:10.1056/nejmoa1608862

Cited by 210 publications

(188 citation statements)

References 24 publications

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“…Compared with standard‐dose influenza vaccine, high‐dose vaccine was also found to reduce hospital admission with respiratory illness and to be cost‐saving . Finally, a recombinant influenza vaccine has been shown to provide a better protection in older adults than the standard quadrivalent, inactivated influenza vaccine . At present, the availability of these newer vaccine products is limited in many settings, and where available, they may be cost‐prohibitive.…”

Section: Discussion and Concluding Remarksmentioning

confidence: 99%

Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

Abusrewil

Algeer²,

Aljifri

et al. 2019

Influenza Resp Viruses

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The Middle‐East and Africa Influenza Surveillance Network ( MENA ‐ ISN ), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA ‐ ISN countries. Data were presented at the 8th MENA ‐ ISN meeting, organized by the Mérieux Foundation that was held on 10‐11 April 2018 in Cairo, Egypt. The meeting included MENA ‐ ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high‐risk groups (children under‐5, elderly, pregnant women and immunosuppressed individuals) in the MENA ‐ ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza‐related morbidity and mortality especially among the most vulnerable groups of the population.

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Section: Discussion and Concluding Remarksmentioning

confidence: 99%

Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

Abusrewil

Algeer²,

Aljifri

et al. 2019

Influenza Resp Viruses

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“…Because the response to influenza M1 and NP, correlates with protection in both CD4 [68] and CD8 T cells [69], these internal proteins will be a necessary component of new vaccines for older adults. These internal proteins are absent in influenza subunit vaccines (HA +/− neuraminidase), so alternative mechanisms including antibody-mediated protection [106] may explain the enhanced protection of adjuvanted [57] and recombinant HA [107] formulations in older adults. A large randomized clinical trial of an AS03-adjuvanted influenza vaccine in older adults also showed enhanced protection against the influenza A/H3N2 vaccine strain compared to the unadjuvanted formulation [108], and this enhanced protection was comparable to that found in the randomized trial of high-dose influenza vaccine [109].…”

Section: The Role Of Influenza Internal Proteins and Adjuvants In Newmentioning

confidence: 99%

The immune response to influenza in older humans: beyond immune senescence

et al. 2020

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Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cellmediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (≥2) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro-and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage.

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“…However, evidence for the effectiveness of these vaccines relative to those produced in eggs is 284 limited given that few head-to-head trials have been performed. One of these trials was carried out 285 during the 2014-2015 season with predominant circulation of antigenically drifted influenza A(H3N2), 286 and found 30% higher relative efficacy in older adults for a recombinant hemagglutinin-based vaccine 287 compared to standard egg-grown inactivated influenza vaccine [29]. Vaccines grown in eggs and in cell-288 culture were found to have similar efficacy overall in a placebo controlled trial carried out in [2007][2008]289 but only the cell-culture derived vaccine demonstrated statistically significant efficacy against influenza 290 A(H3N2) [30].…”

Section: Discussion 234mentioning

confidence: 99%

Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season

Levine

Martin

Petrie

et al. 2018

Preprint

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BackgroundThe 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.MethodsSerum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.ResultsMN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.ConclusionAlthough individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.

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Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older

Abstract: RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness among older adults. (Funded by Protein Sciences; ClinicalTrials.gov number, NCT02285998 .).

Cited by 210 publications

References 24 publications

Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

Influenza surveillance in Middle East, North, East and South Africa: Report of the 8th MENA Influenza Stakeholders Network

The immune response to influenza in older humans: beyond immune senescence

Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season

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