scholarly journals Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial

2019 ◽  
Vol 71 (7) ◽  
pp. 1704-1714 ◽  
Author(s):  
Benjamin J Cowling ◽  
Ranawaka A P M Perera ◽  
Sophie A Valkenburg ◽  
Nancy H L Leung ◽  
A Danielle Iuliano ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Standard Dose ◽  
Community Dwelling ◽  
Quadrivalent Vaccine ◽  
High Dose ◽  
Cell Responses ◽  
Trivalent Vaccine ◽  
Community Dwelling Older Adults ◽  
Dose Vaccine

Abstract Background Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. Methods Community-dwelling older adults aged 65–82 years in Hong Kong were randomly allocated (October 2017–January 2018) to receive 2017–2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. Results Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. Conclusions In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. Clinical Trials Registration NCT03330132.

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

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.

scholarly journals Key Determinants of Cell-Mediated Immune Responses: A Randomized Trial of High Dose Vs. Standard Dose Split-Virus Influenza Vaccine in Older Adults

2021 ◽  
Vol 2 ◽  
Author(s):  
Chris P. Verschoor ◽  
Laura Haynes ◽  
Graham Pawelec ◽  
Mark Loeb ◽  
Melissa K. Andrew ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Standard Dose ◽  
Serum Antibody ◽  
High Dose ◽  
Post Vaccination ◽  
Antibody Titers ◽  
Virus Influenza

Background: Efforts to improve influenza vaccine effectiveness in older adults have resulted in some successes, such as the introduction of high-dose split-virus influenza vaccine (HD-SVV), yet studies of cell-mediated immune responses to these vaccines remain limited. We have shown that granzyme B (GrB) activity in influenza A/H3N2 challenged peripheral blood mononuclear cells (PBMC) correlates with protection against influenza following standard dose vaccination (SD-SVV) in older adults. Further, the interferon-γ (IFNγ) to interleukin-10 (IL-10) ratio can be a correlate of protection.Methods: In a double-blind trial (ClinicalTrials.gov NCT02297542) older adults (≥65 years, n = 582) were randomized to receive SD-SVV or HD-SVV (Fluzone®) from 2014/15 to 2017/18. Young adults (20–40 years, n = 79) received SD-SVV. At 0, 4, 10, and 20 weeks post-vaccination, serum antibody titers, IFNγ, IL-10, and inducible GrB (iGrB) were measured in ex vivo influenza-challenged PBMC. iGrB is defined as the fold change in GrB activity from baseline levels (bGrB) in circulating T cells. Responses of older adults were compared to younger controls, and in older adults, we analyzed effects of age, sex, cytomegalovirus (CMV) serostatus, frailty, and vaccine dose.Results: Prior to vaccination, younger compared to older adults produced significantly higher IFNγ, IL-10, and iGrB levels. Relative to SD-SVV recipients, older HD-SVV recipients exhibited significantly lower IFNγ:IL-10 ratios at 4 weeks post-vaccination. In contrast, IFNγ and iGrB levels were higher in younger SD vs. older SD or HD recipients; only the HD group showed a significant IFNγ response to vaccination compared to the SD groups; all three groups showed a significant iGrB response to vaccination. In a regression analysis, frailty was associated with lower IFNγ levels, whereas female sex and HD-SVV with higher IL-10 levels. Age and SD-SVV were associated with lower iGrB levels. The effect of prior season influenza vaccination was decreased iGrB levels, and increased IFNγ and IL-10 levels, which correlated with influenza A/H3N2 hemagglutination inhibition antibody titers.Conclusion: Overall, HD-SVV amplified the IL-10 response consistent with enhanced antibody responses, with little effect on the iGrB response relative to SD-SVV in either younger or older adults. These results suggest that enhanced protection with HD-SVV is largely antibody-mediated.Clinical Trial Registration: ClinicalTrials.gov (NCT02297542).

scholarly journals 25. Effectiveness of High Dose Influenza Vaccine in HIV-positive Patients for the Winter 2017–2018 Season

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S36-S37
Author(s):  
Mikiro Kato ◽  
Tori Kunkel ◽  
David Bram ◽  
Jessica Newman ◽  
Angela Lopez ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Sore Throat ◽  
Standard Dose ◽  
Winter Season ◽  
Panel Member ◽  
Vaccine Dose ◽  
Quadrivalent Vaccine ◽  
High Dose ◽  
Vaccine Type ◽  
Dose Vaccine

Abstract Background Antibody response after high dose influenza vaccine (HDIV) approved for age ≥ 65 years, is superior to a standard-dose vaccine in HIV-infected persons. We report the effectiveness data of HDIV compared to the standard dose quadrivalent vaccine (SDIV) in our HIV clinic. Methods We conducted a retrospective cohort study at the University of Kansas Medical Center to evaluate the effectiveness of HDIV in HIV-infected patients during the 2017–2018 influenza season. A phone survey was utilized to verify vaccination status and interval development of influenza-like illness (ILI). A modified CDC definition of ILI (mCDC ILI = fever and cough, sore throat or shortness of breath (SOB)) and a broader protocol defined ILI (PD ILI = sore throat, cough or SOB with either fever, chills, headache or myalgia) were utilized. The electronic medical record was reviewed to confirm vaccine type and influenza testing when available. Results Of 560 HIV-infected patients in the clinic, 219 (39.1%) were available and willing to participate (197 males, 21 females, 1 transgender female). The median age was 53 years and BMI 27.2 kg/m2. Five percent had CD4< 200 cells/uL, and 13.7% had an HIV viral load > 40 copies/mL. HDIV was given to 119 (54.3%), SDIV to 77 (35.2%) and 23 (10.5%) were not vaccinated (Table 1). A mCDC ILI occurred in 8 (10.4%) in the SDIV group compared to 6 (5.0%) in the HDIV group (p=0.16). A PD ILI was reported in 16 (20.8%) in the SDIV group compared to 12 (10.1%) in the HDIV group (p=0.04). There was no difference in confirmed influenza cases between the two groups (Table 2). On logistic regression only vaccine dose (SDIV OR 2.34 95% CI 1.04–5.37, p=0.04) and age in years (OR 0.97, 95% CI 0.94–1.0, p=0.045) were associated with PD ILI. HDIV remained protective after adjustment for age. Vaccine side effects were mild and occurred in 11/77 (14.3%) in the SDIV group compared to 13/119 (10.9%) in the HDIV group (p=0.5). Conclusion During the 2017–2018 winter season, the CDC reported an influenza attack rate of 14.7% in adults in the US and overall vaccine effectiveness of 38%. Our study demonstrated a 50% reduction in ILI with the HDIV compared to the standard-dose vaccine in HIV-infected patients. A larger prospective randomized control trial is warranted. Disclosures Wissam El Atrouni, MD, ViiV (Advisor or Review Panel member)

Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults

2020 ◽  
Vol 222 (8) ◽  
pp. 1383-1391
Author(s):  
Benjamin J Cowling ◽  
Mark G Thompson ◽  
Tiffany W Y Ng ◽  
Vicky J Fang ◽  
Ranawaka A P M Perera ◽  
...  
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Standard Dose ◽  
Controlled Trial ◽  
Community Dwelling ◽  
Influenza Vaccines ◽  
High Dose ◽  
Systemic Reactions ◽  
Local Reactions ◽  
Systemic Symptoms

Abstract Background We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine. Methods We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017–2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination. Results Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01–3.38) for A(H1N1) than in those who did not report feverishness. Conclusions Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population. Clinical Trials Registration NCT03330132.

scholarly journals Immunogenicity of standard, high-dose, MF59-adjuvanted, and recombinant-HA seasonal influenza vaccination in older adults

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Athena P. Y. Li ◽  
Carolyn A. Cohen ◽  
Nancy H. L. Leung ◽  
Vicky J. Fang ◽  
Shivaprakash Gangappa ◽  
...  
Keyword(s):  
Older Adults ◽  
T Cell ◽  
Nk Cell ◽  
Standard Dose ◽  
Controlled Trial ◽  
T Cell Responses ◽  
High Dose ◽  
Adcc Activity ◽  
Vaccine Platform ◽  
Cell Responses

AbstractThe vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use of vaccines with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses of S-IIV versus enhanced vaccines (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), and recombinant-hemagglutinin (HA) (R-eIIV). All vaccines induced comparable H3-HA-specific IgG and elevated antibody-dependent cellular cytotoxicity (ADCC) activity at day 30 post vaccination. H3-HA-specific ADCC responses were greatest following H-eIIV. Only A-eIIV increased H3-HA-IgG avidity, HA-stalk IgG and ADCC activity. eIIVs also increased polyfunctional CD4+ and CD8+ T cell responses, while cellular immune responses were skewed toward single-cytokine-producing T cells among S-IIV subjects. Our study provides further immunological evidence for the preferential use of eIIVs in older adults as each vaccine platform had an advantage over the standard-dose vaccine in terms of NK cell activation, HA-stalk antibodies, and T cell responses.

scholarly journals Evaluation of a Collaborative Care Management Program for Community-Dwelling Older Adults on High-Dose Opiates

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 206-207
Author(s):  
Shahrzad Mavandadi ◽  
Kristin Foust-Montague ◽  
Elizabeth Grecco ◽  
David Oslin ◽  
Joel Streim
Keyword(s):  
Older Adults ◽  
Collaborative Care ◽  
Community Dwelling ◽  
Equivalent Dose ◽  
High Dose ◽  
Assistance Program ◽  
Opioid Dose ◽  
Community Dwelling Older Adults ◽  
Morphine Equivalent ◽  
Dose Reductions

Abstract Treating pain in later life is complex, and there are significant safety risks associated with the use of analgesics, particularly opioids. This study examined preliminary results from a pilot study of a telephone-delivered collaborative care service designed for community-dwelling older adults with chronic pain receiving prescriptions for high doses of opioids (i.e., >120 mg morphine-equivalent dose). Eighty-two older adults referred by the Pennsylvania Department of Aging’s pharmaceutical assistance program for low-income seniors (PACE/PACENET) were eligible and enrolled in the program (i.e., the University of Pennsylvania/PACE Behavioral Health Laboratory). Patients were on average 73.5 (+/-6.1) years old, and the majority were white (91%) and female (70%). Patients completed a comprehensive baseline clinical assessment capturing their mental health, cognition, pain and functional status, as well as self-reported daily opioid dose and biopsychosocial needs. Patients were considered engaged in the program if they completed 2+ additional follow-up contacts with a care manager. During these contacts, care managers offered individualized treatment planning, with the goal of opioid dose reduction to safer levels. Of the 82 patients completing the baseline, 53 (65%) engaged in the program. At their last clinical contact, 91% of engaged patients achieved dose reductions (with 66% achieving dose reductions of >20% and 30% reporting doses <120 mg morphine-equivalent dose). Engaged patients also reported significant reductions in pain severity (p=0.05) and depressive symptoms (p=0.003) at the last contact relative to baseline. Findings support the feasibility of a community-based, collaborative care model for pain management and suggest the potential for positive treatment outcomes.

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