The Vaccination and Travel Medicine Center, Poliklinika II, Bratří Štefanu 895, Hradec Králové 500 03, Czech Republic.
BMC Infect Dis. 2013 May 20;13:224. doi: 10.1186/1471-2334-13-224.
Two phylogenetic lineages of influenza B virus coexist and circulate in the human population (B/Yamagata and B/Victoria) but only one B-strain is included in each seasonal vaccine. Mismatch regularly occurs between the recommended and circulating B-strain. Inclusion of both lineages in vaccines may offer better protection against influenza.
This study (NCT00714285) assessed the immunogenicity and safety of two candidate quadrivalent influenza vaccines (QIV) containing two A- and two B-strains (one from each lineage) in adults (18-60 years). Subjects were randomized and stratified by age to receive either QIV (non-adjuvanted or low-dose adjuvanted [LD QIV-AS]) or trivalent influenza vaccine (TIV, non-adjuvanted or low-dose adjuvanted [LD TIV-AS]), N = 105 in all treatment groups. The study evaluated the statistical non-inferiority of the immunological response elicited by QIV and LD QIV-AS versus TIV and LD TIV-AS and the statistical superiority of the response elicited by the quadrivalent vaccines against the B-strain (B/Jiangsu) not included in the TIV.
Pre-defined non-inferiority and superiority criteria were reached for both QIVs compared to the TIVs. On Day 21 in all vaccine groups SCRs were ≥54.8%, SPRs ≥88.5% and SCFs ≥5.4 for the A strains and B strain included in all vaccines (B/Malaysia). This fulfilled the European (CHMP) and the US (CBER) licensing criteria for the assessment of influenza vaccines in adults (CHMP criteria: SCR > 40%, SPR > 70%, SCF > 2; CBER criteria: LL of 95% CI for SPR ≥ 70% or SCR ≥ 40%). Only the QIVs met the CHMP and CBER criteria for the B/Jiangsu strain. In the QIV and LD-QIV-AS groups, the SCFs were 9.1 and 8.1, respectively and the SPRs were 98.1% and 95.2%, whereas for the TIV and LD-TIV-AS groups, the SCFs were 2.3 and 2.5, respectively, and the SPRs were 75.0% and 63.8%, with the LLs of the 95% CI <70% for SPR and <40% for SCR.
Addition of a fourth strain did not impact the immune response elicited by the three original strains contained in the TIV. A clear immunological benefit was seen with the QIV formulation for the second B-strain, indicating that quadrivalent vaccines could provide broader protection against influenza.
ClinicalTrials.gov: NCT00714285.
乙型流感病毒存在两个进化枝（B/Yamagata 和 B/Victoria）在人群中共同传播和循环，但每个季节性疫苗中仅包含一种 B 株系。推荐株和流行株之间经常出现不匹配的情况。在疫苗中包含两种谱系可能会提供更好的流感保护。
这项研究（NCT00714285）评估了两种候选四价流感疫苗（QIV）在成人（18-60 岁）中的免疫原性和安全性，这两种疫苗均含有两种 A 株和两种 B 株（每种谱系各一种）。受试者随机分组并按年龄分层，分别接受 QIV（无佐剂或低剂量佐剂 [LD QIV-AS]）或三价流感疫苗（TIV，无佐剂或低剂量佐剂 [LD TIV-AS]），每组各有 105 名受试者。该研究评估了 QIV 和 LD QIV-AS 与 TIV 和 LD TIV-AS 引起的免疫反应的统计学非劣效性，以及四价疫苗对 TIV 中未包含的 B 株系（B/Jiangsu）引起的免疫反应的统计学优势。
与 TIV 相比，两种 QIV 均达到了预先设定的非劣效性和优越性标准。在所有疫苗组中，第 21 天的 SCR 均≥54.8%，SPR≥88.5%，SCF≥5.4%，用于评估所有疫苗中包含的 A 株系和 B 株系（所有疫苗中的 B/Malaysia）。这满足了欧洲（CHMP）和美国（CBER）对成人流感疫苗评估的许可标准（CHMP 标准：SCR>40%，SPR>70%，SCF>2；CBER 标准：SPR≥70%或 SCR≥40%的 95%CI 的下限）。只有 QIV 满足了 B/Jiangsu 株系的 CHMP 和 CBER 标准。在 QIV 和 LD-QIV-AS 组中，SCF 分别为 9.1 和 8.1，SPR 分别为 98.1%和 95.2%，而在 TIV 和 LD-TIV-AS 组中，SCF 分别为 2.3 和 2.5，SPR 分别为 75.0%和 63.8%，SPR 和 SCR 的 95%CI 下限<70%和<40%。
添加第四种菌株不会影响 TIV 中包含的三种原始菌株引起的免疫反应。四价疫苗在第二种 B 株系上产生了明显的免疫益处，表明四价疫苗可以提供更广泛的流感保护。
ClinicalTrials.gov：NCT00714285。
