Clinical trial to assess immunogenicity of high-dose, adjuvanted, and recombinant influenza vaccines against cell-grown A(H3N2) viruses in adults 65 to 74 years, 2017–2018

Belongia, Edward A; Levine, Min Z.; Olaiya, Oluwatosin; Gross, F. Liaini; King, Jennifer; Flannery, Brendan; McLean, Huong Q.

doi:10.1016/j.vaccine.2020.02.055

Cited by 12 publications

(20 citation statements)

References 19 publications

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“…Prelicensure trials evaluating these vaccines measured antibody responses to a variety of targets including egg-grown viruses, cell-grown viruses, and baculovirus expression vector systems (BEVS)-derived antigen [13][14][15][16]. Although several recent trials have documented improved humoral immune responses to RIV4 compared to IIV4 in adults 18-64 years [17] and ≥65 years of age [18,19], RIV4 and ccIIV4 have not been evaluated against IIV4 in highly influenza-vaccinated working-age adult populations in whom immune responses to influenza vaccination may be blunted over time [20]. To date, there are few data directly comparing the immunogenicity of cell-based and recombinant influenza vaccines to egg-based vaccines using the same immunogenicity outcome measures against the same antigenic targets.…”

mentioning

confidence: 99%

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18–64 Years: A Randomized Open-Label Trial

Dawood

Naleway

Flannery

et al. 2021

Clinical Infectious Diseases

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Background RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among HCP aged 18-64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. Methods During the 2018-2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had sera collected pre-vaccination, 1 and 6 months post-vaccination. Sera were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. Results 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95%CI 1.2-1.9) for A/H1N1, 3.0 (95%CI 2.4-3.7) for A/H3N2, 1.1 (95%CI 0.9-1.4) for B/Yamagata, and 1.1 (95%CI 0.9-1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. Conclusion RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against three of four cell-grown vaccine strains 1 month post-vaccination, suggesting a possible additional benefit from RIV4.

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confidence: 99%

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18–64 Years: A Randomized Open-Label Trial

Dawood

Naleway

Flannery

et al. 2021

Clinical Infectious Diseases

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“…The study by Nachbagaeur et al 78 supports the hypothesis that a recombinant vaccine results in increased titre of broadly neutralising HA stem-reactive antibodies and that these immune responses increase with age 78 . This increase with age is possibly due to repeated exposure to divergent influenza viruses similar to the multiple A/H3N2 virus strains evaluated by Belongia et al 82 . Therefore, vaccine constructs that preserve the highly conserved HA stem can protect against drifted viruses and thus may confer a greater breadth of protection against influenza.…”

Section: The N-linked Glycan Structure Of Recombinant Ha Produced In Insect Cells Differs Significantly From Ha In Other Influenza Vaccinmentioning

confidence: 85%

“…RIV4 has a unique ability to induce broadly cross-reactive antibody responses to antigenically drifted A/H3N2 viruses in humans. In a small study by Belongia et al 82 , participants aged 65–74 years were immunised with RIV4, a high-dose split-virion inactivated trivalent influenza vaccine (Fluzone ® High Dose, Sanofi Pasteur; HD-IIV3) or adjuvanted-IIV3 (aIIV3) 82 . Participant sera were tested against four A/H3N2 viruses including a cell-propagated reference vaccine strain, two circulating viruses and an antigenically advanced virus with evidence of antigenic drift.…”

Section: The N-linked Glycan Structure Of Recombinant Ha Produced In Insect Cells Differs Significantly From Ha In Other Influenza Vaccinmentioning

confidence: 99%

Unique features of a recombinant haemagglutinin influenza vaccine that influence vaccine performance

2021

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The influenza vaccine field has been constantly evolving to improve the speed, scalability, and flexibility of manufacturing, and to improve the breadth and longevity of the protective immune response across age groups, giving rise to an array of next generation vaccines in development. Among these, the recombinant influenza vaccine tetravalent (RIV4), using a baculovirus expression vector system to express recombinant haemagglutinin (rHA) in insect cells, is the only one to have reached the market and has been studied extensively. We describe how the unique structural features of rHA in RIV4 improve protective immune responses compared to conventional influenza vaccines made from propagated influenza virus. In addition to the sequence integrity, characteristic of recombinant proteins, unique post-translational processing of the rHA in insect cells instills favourable tertiary and quaternary structural features. The absence of protease-driven cleavage and addition of simple N-linked glycans help to preserve and expose certain conserved epitopes on HA molecules, which are likely responsible for the high levels of broadly cross-reactive and protective antibodies with rare specificities observed with RIV4. Furthermore, the presence of uniform compact HA oligomers and absence of egg proteins, viral RNA or process impurities, typically found in conventional vaccines, are expected to eliminate potential adverse reactions to these components in susceptible individuals with the use of RIV4. These distinct structural features and purity of the recombinant HA vaccine thus provide a number of benefits in vaccine performance which can be extended to other viral targets, such as for COVID-19.

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“…Our LCI data matched the relative rate reported based on HIS data between 2011/2012 and 2015/2016. There is no data on 2010/2011 in HIS, however, the estimated number of patients aged 60 years and older with medical visit for influenza in 2010/2011 was less than half of those in 2011/2012 [ 52 ]. The consistency of different study results may suggest the legitimacy of our data in the 2011/2012 season but additional investigations to explain the increasing trend, particularly into the frequency and criteria for confirmatory diagnostic use, are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…al., reported that, in France, in-hospital mortality associated with influenza was ~6%, and that increased to 18% among patients admitted to the ICU and increased with age because of differences in healthcare systems, threshold for hospitalization and ICU admission, underlying health characteristics of the various populations, and how the data are presented (which in most cases do not report by small age groups). Influenza vaccination is the cornerstone to prevent influenza in the community, and despite low to moderate vaccine effectiveness documented from year to year, there are vaccines that can afford better protection to high-risk populations and the elderly but they are not yet available in Japan [49][50][51][52].…”

Section: Plos Onementioning

confidence: 99%

Seasonal influenza, its complications and related healthcare resource utilization among people 60 years and older: A descriptive retrospective study in Japan

et al. 2022

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Evidence suggests that older people aged ≥65 years and those aged 60–64 years with chronic medical conditions are at higher risk of developing severe complications due to influenza virus infection when compared with young, healthy adults. Although seasonal influenza is monitored through a nationwide passive surveillance in Japan, influenza related outcomes and medical resource consumption have not been fully documented. This retrospective database study aimed to describe the epidemiological and clinical characteristics of medically attended influenza cases aged ≥60 years and the associated medical resource consumption in Japan. We used clinically diagnosed influenza (CDI) based on the international classification of disease codes, and laboratory-confirmed influenza (LCI) based on influenza test results, to identify the patient population during a total of nine seasons (2010/2011 to 2018/2019). A total of 372,356 CDI and 31,122 LCI cases were identified from 77 medical institutions. The highest numbers of medically-attended influenza episodes were in patients aged 65–74 years and 75–84 years. On average, across seasons, 5.9% of all-cause hospitalizations were attributable to CDI and 0.4% were LCI. Influenza viruses type A and B co-circulated annually in varying degree of intensity and were associated with similar level of complications, including cardiovascular-related. Oxygen therapy increased with age; by contrast, mechanical ventilation, dialysis, blood transfusion, and intensive care unit admission were higher in the younger groups. In-hospital mortality for inpatients aged ≥ 85 years with CDI and LCI were 18.6% and 15.5%, respectively. Considering the burden associated with medically-attended influenza in this population, influenza prevention, laboratory confirmation and clinical management should be emphasized by general practicians and specialists like cardiologists to protect this aging population.

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Clinical trial to assess immunogenicity of high-dose, adjuvanted, and recombinant influenza vaccines against cell-grown A(H3N2) viruses in adults 65 to 74 years, 2017–2018

Cited by 12 publications

References 19 publications

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18–64 Years: A Randomized Open-Label Trial

Comparison of the Immunogenicity of Cell Culture-Based and Recombinant Quadrivalent Influenza Vaccines to Conventional Egg-Based Quadrivalent Influenza Vaccines Among Healthcare Personnel Aged 18–64 Years: A Randomized Open-Label Trial

Unique features of a recombinant haemagglutinin influenza vaccine that influence vaccine performance

Seasonal influenza, its complications and related healthcare resource utilization among people 60 years and older: A descriptive retrospective study in Japan

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