Relative Effectiveness of Cell-Cultured versus Egg-Based Seasonal Influenza Vaccines in Preventing Influenza-Related Outcomes in Subjects 18 Years Old or Older: A Systematic Review and Meta-Analysis

Avian mutations in vaccine strains obtained from embryonated eggs could impair vaccine effectiveness. We performed a systematic review and meta-analysis of the adjusted relative vaccine effectiveness (arVE) of seed cell-cultured influenza vaccines (ccIV) compared to egg-based influenza vaccines (eIV) in preventing laboratory-confirmed influenza related outcomes (IRO) or IRO by clinical codes, in subjects 18 and over. We completed the literature search in January 2021; applied exclusion criteria, evaluated risk of bias of the evidence, and performed heterogeneity, publication bias, qualitative, quantitative and sensitivity analyses. All estimates were computed using a random approach. International Prospective Register of Systematic Reviews, CRD42021228290. We identified 12 publications that reported 26 adjusted arVE results. Five publications reported 13 laboratory confirmed arVE and seven reported 13 code-ascertained arVE. Nine publications with 22 results were at low risk of bias. Heterogeneity was explained by season. We found a significant 11% (8 to 14%) adjusted arVE favoring ccIV in preventing any IRO in the 2017–2018 influenza season. The arVE was 3% (−2% to 7%) in the 2018–2019 influenza season. We found moderate evidence of a significant advantage of the ccIV in preventing IRO, compared to eIV, in a well-matched A(H3N2) predominant season.

STUDI EFEKTIVITAS VAKSIN INFLUENZA: UPDATED REVIEW

Influenza is caused by a rapidly mutating viruse that consists of 2 types, namely type A with the H1N1 and H3N2 genotypes and type B. Influenza caused global mortality with 250,000-500,000 death in 2009. The effectiveness of vaccines also changes regarding the mutation of influenza viruses, however, in the development and utilization of influenza vaccines should be supported by the economic status of a country. Up to now, there are many countries that have not prioritized the utilization of influenza vaccines. The target of influenza vaccination are children and adults (> 60 years old). The purpose of this review was to determine the effectiveness of influenza vaccines from various countries and categorized based on their income. This review used Medline, Elsevier, and BMC Public Health as the database with the keywords "Effectiveness" and "Influenza vaccine". Then, the articles are selected based on inclusion and exclusion criteria. Based on the initial search there are 784 articles that match the keywords, and only 13 articles met the criteria. These articles are classified based on the center of the study in order to classify based on their national income; 5 studies in high income countries, 5 studies in upper-middle income countries, 3 studies in lower-middle income countries, and 1 study in low income countries. The results showed that the administration of influenza vaccine in high income and upper-middle income countries is quite effective for type A H1N1 genotypes, where as H3N2 is less effective. In the lower-middle income countries, the utilization of vaccines with type A H3N2 genotypes was effective, however, in the low-income countries, the effectiveness of vaccines has not been justified due to the limited study of type of influenza and the administration of influenza vaccines in those countries.

Relative Effectiveness of Cell-Cultured versus Egg-Based Seasonal Influenza Vaccines in Preventing Influenza-Related Outcomes in Subjects 18 Years Old or Older: A Systematic Review and Meta-Analysis

Avian mutations in vaccine strains obtained from embryonated eggs could impair vaccine effec-tiveness. We performed a systematic review and meta-analysis of the adjusted relative vaccine effectiveness (arVE) of seed cell-cultured influenza vaccines (ccIV) compared to egg-based influ-enza vaccines (eIV) in preventing laboratory-confirmed influenza related outcomes (IRO) or IRO by clinical codes, in subjects 18 and over. We completed the literature search in January 2021; ap-plied exclusion criteria, evaluated risk of bias of the evidence, and performed heterogeneity, pub-lication bias, qualitative, quantitative and sensitivity analyses. All estimates were computed us-ing a random approach. International Prospective Register of Systematic Reviews, CRD42021228290. We identified 12 publications that reported 26 adjusted arVE results. Five publications reported 13 laboratory confirmed arVE and seven reported 13 code-ascertained arVE. Nine publications with 22 results were at low risk of bias. Heterogeneity was explained by season and risk of bias. We found a significant 11% (8 to 14%) adjusted arVE favoring ccIV in preventing any IRO in the 2017-2018 influenza season. The arVE was 3% (-01 to 7%) in the 2018-2019 influenza season. We found moderate evidence of a significant advantage of the ccIV in preventing IRO, compared to eIV, in a well-matched A(H3N2) predominant season.

Potentiating Lung Mucosal Immunity Through Intranasal Vaccination

Yearly administration of influenza vaccines is our best available tool for controlling influenza virus spread. However, both practical and immunological factors sometimes result in sub-optimal vaccine efficacy. The call for improved, or even universal, influenza vaccines within the field has led to development of pre-clinical and clinical vaccine candidates that aim to address limitations of current influenza vaccine approaches. Here, we consider the route of immunization as a critical factor in eliciting tissue resident memory (Trm) populations that are not a target of current licensed intramuscular vaccines. Intranasal vaccination has the potential to boost tissue resident B and T cell populations that reside within specific niches of the upper and lower respiratory tract. Within these niches, Trm cells are poised to respond rapidly to pathogen re-encounter by nature of their anatomic localization and their ability to rapidly deliver anti-pathogen effector functions. Unique features of mucosal immunity in the upper and lower respiratory tracts suggest that antigen localized to these regions is required for the elicitation of protective B and T cell immunity at these sites and will need to be considered as an important attribute of a rationally designed intranasal vaccine. Finally, we discuss outstanding questions and areas of future inquiry in the field of lung mucosal immunity.

Interpretation of Relative Efficacy and Effectiveness for Influenza Vaccines

Relative vaccine effectiveness (rVE) are metrics commonly reported to compare absolute VE (aVE) of two vaccine products. Estimates of rVE for enhanced influenza vaccines (eIV) vs. standard inactivated influenza vaccine (IIV) have been assessed across different seasons, influenza-specific endpoints, and nonspecific endpoints (e.g., all-cause cardiovascular hospitalizations). To illustrate the challenges of comparability across studies, we conducted a scenario analysis to evaluate the effects of varying absolute VE (aVE) of IIV (i.e., as compared with placebo) on the interpretation of rVE of eIV vs IIV. We show that estimates of rVE might not be comparable across studies because additional benefits commensurate with a given estimate of rVE are dependent on the aVE for the comparator vaccine, which can depend on factors such as host response to vaccine, virus type, and clinical endpoint evaluated. These findings have implications for interpretation of rVE across studies and for sample size considerations in future trials.