Effectiveness of influenza vaccine in reducing influenza-associated hospitalizations and deaths among the elderly population; Lazio region, Italy, season 2016-2017.
流感疫苗在减少老年人群流感相关住院和死亡中的有效性; 意大利拉齐奥地区，2016-2017 季节。
- 作者列表："Fabiani M","Volpe E","Faraone M","Bella A","Pezzotti P","Chini F
:Background: This study aimed to estimate influenza vaccine effectiveness (VE) in preventing influenza-related deaths and hospitalizations in the elderly population.Methods: We retrospectively analyzed the cohort of 1,251,218 elderly aged ≥65 years who were residing in the Lazio region in 2016-2017. We estimated influenza VE using the Cox proportional hazards model, adjusting for demographic characteristics, pre-existing health-risk conditions, and prior vaccinations.Results: Estimated VE was 14% (95% confidence interval (CI): 11 to 17); 26% (95%CI: 19 to 33) in preventing influenza-related deaths and 13% (95%CI: 10 to 16) in preventing influenza-related hospitalizations. Seasonal VE was higher in the elderly vaccinated in prior seasons (VE=20%, 95%CI: 17 to 23). We found no significant differences in effectiveness by vaccine type, although the MF59-adjuvanted vaccine appeared more effective than other vaccines in individuals aged ≥75 years, particularly in those aged ≥90 years (VE=18%, 95%CI: 9 to 26).Conclusions: Although VE was low, vaccination still provided benefits in preventing influenza-related hospitalizations and deaths in the elderly, particularly among those vaccinated in prior seasons. Efforts should therefore be made to improve vaccine uptake and the utilization of vaccines with greater effectiveness in the oldest elderly (e.g., high-dose and adjuvanted cell-based vaccines).
背景: 本研究旨在评估流感疫苗在老年人群中预防流感相关死亡和住院的有效性 (VE)。方法: 我们回顾性分析了 1,251,218-2016 年居住在拉齐奥地区的 2017 名 ≥ 65 岁老年人的队列。我们使用 Cox 比例风险模型估计了流感 VE，调整了人口统计学特征、预先存在的健康风险状况和既往接种疫苗。结果: 估计 VE 为 14% (95% 置信区间 (CI): 11 至 17); 26% (95% CI: 19 至 33) 在预防流感相关死亡和 13% (95% CI: 10 至 16)预防流感相关住院。在以前的季节接种疫苗的老年人中季节性 VE 较高 (VE = 20%，95% CI: 17 ~ 23)。我们没有发现不同疫苗类型的有效性有显著差异，尽管 MF59-佐剂疫苗在年龄 ≥ 75 岁的个体中似乎比其他疫苗更有效，特别是在年龄 ≥ 90 岁的个体中 (VE = 18%, 95% CI: 9 至 26)。结论: 虽然 VE 很低,接种疫苗仍然在预防老年人流感相关住院和死亡方面提供了益处，特别是在以前季节接种疫苗的人群中。因此，应努力提高疫苗的摄取和对年龄最大的老年人使用更有效的疫苗 (例如，高剂量和基于佐剂的细胞疫苗)。
METHODS:BACKGROUND:From 2015/16 through 2017/18, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in two-year-olds was estimated for all three seasons. METHODS:Each season, a nationwide register-based cohort study was conducted. The study population comprised 60,088 children in 2015/16, 60,860 children in 2016/17 and 60,345 children in 2017/18. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. RESULTS:From 2015/16 through 2017/18, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2%-69.0%), 20.3% (-12.7% to 43.6%) and 30.5% (10.9%-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9%-89.8%), 24.5% (-29.8% to 56.1%) and -20.1% (-61.5% to 10.7%). Neither of the influenza vaccines clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. CONCLUSIONS:To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates expressing also overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.
METHODS::Intranasally administered influenza vaccines could be more effective than injected vaccines, since intranasal vaccination can induce virus-specific IgA antibodies in the upper respiratory tract, which is the initial site of infection. In the current study, immune responses elicited by an intranasal inactivated H5 influenza vaccine were evaluated in healthy H5 influenza virus-naive individuals. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy-vinyl polymer (CVP), had a notable impact on the induction of nasal IgA antibody responses but not serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific helper T (Th) cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against H5 influenza viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses. This article is protected by copyright. All rights reserved.
METHODS:BACKGROUND:Influenza is an important public health problem and existing vaccines are not completely protective. New vaccines that protect by alternative mechanisms are needed to improve efficacy of influenza vaccines. In 2015, we did a phase 1 trial of an oral influenza vaccine, VXA-A1.1. A favourable safety profile and robust immunogenicity results in that trial supported progression of the vaccine to the current phase 2 trial. The aim of this study was to evaluate efficacy of the vaccine in a human influenza challenge model. METHODS:We did a single-site, placebo-controlled and active-controlled, phase 2 study at WCCT Global, Costa Mesa, CA, USA. Eligible individuals had an initial A/California/H1N1 haemagglutination inhibition titre of less than 20 and were aged 18-49 years and in good health. Individuals were randomly assigned (2:2:1) to receive a single immunisation of either 1011 infectious units of VXA-A1.1 (a monovalent tablet vaccine) orally, a full human dose of quadrivalent inactivated influenza vaccine (IIV) via intramuscular injection, or matched placebo. Randomisation was done by computer-generated assignments with block size of five. An unmasked pharmacist provided the appropriate vaccines and placebos to the administrating nurse. Individuals receiving the treatments, investigators, and staff were all masked to group assignments. 90 days after immunisation, individuals without clinically significant symptoms or signs of influenza, an oral temperature of higher than 37·9°C, a positive result for respiratory viral shedding on a Biofire test, and any investigator-assessed contraindications were challenged intranasally with 0·5 mL wild-type A/CA/like(H1N1)pdm09 influenza virus. The primary outcomes were safety, which was assessed in all immunised participants through 365 days, and influenza-positive illness after viral challenge, which was assessed in individuals that received the viral challenge and the required number of assessments post viral challenge. This trial is registered with ClinicalTrials.gov, number NCT02918006. RESULTS:Between Aug 31, 2016, and Jan 23, 2017, 374 individuals were assessed for eligibility, of whom 179 were randomly assigned to receive either VXA-A1.1 (n=71 [one individual did not provide a diary card, thus the solicited events were assessed in 70 individuals]), IIV (n=72), or placebo (n=36). Between Dec 2, 2016, and April 26, 2017, 143 eligible individuals (58 in the VXA-A1.1 group, 54 in the IIV group, and 31 in the placebo group) were challenged with influenza virus. VXA-A1.1 was well tolerated with no serious or medically significant adverse events. The most prevalent solicited adverse events for each of the treatment groups after immunisation were headache in the VXA-A1.1 (in five [7%] of 70 participants) and placebo (in seven [19%] of 36 participants) groups and tenderness at injection site in the IIV group (in 19 [26%] of 72 participants) Influenza-positive illness after challenge was detected in 17 (29%) of 58 individuals in the VXA-A1.1 group, 19 (35%) of 54 in the IIV group, and 15 (48%) of 31 in the placebo group. INTERPRETATION:Orally administered VXA-A1.1 was well tolerated and generated protective immunity against virus shedding, similar to a licensed intramuscular IIV. These results represent a major step forward in developing a safe and effective oral influenza vaccine. FUNDING:Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority.