探討成年人施打季節性流感疫苗後之抗B型流感病毒血凝素病毒血凝素B細胞與抗體反應

Abstract

B 型流感病毒與 A 型流感病毒共同傳播導致全球季節性流感爆發。流感病毒有兩 種主要的表面蛋白，血凝素 hemagglutinin (HA) 和神經氨酸酶 neuraminidase。根 據 HA 的抗原差異，B 型流感病毒被分為兩個抗原性不同的譜系，Victoria 譜系和 Yamagata 譜系。季節性流感疫苗被廣泛認為是一種有效引起針對流感病毒的保護 性免疫反應的方法，而其保護作用主要由抗 HA 的抗體介導。然而，目前對於人 類接種疫苗後的抗 B 型流感病毒 HA 的 B 細胞和抗體反應細節仍不清楚。在這項 研究中，我們從兩名接種 2022-2023 年北半球四價流感疫苗後的成年人身上建構出 B 細胞衍生之抗 B 型流感病毒 HA 的單株抗體庫，我們檢測到的抗 B 型流感病毒 HA 抗體反應，其中包括了 Victoria 譜系病毒特異性抗體、Yamagata 譜系病毒特異 性抗體和交叉反應性抗體。我們也檢測到可以結合在近期流行的 Victoria 譜系或是 Yamagata 譜系病毒 HA 頭部結構的特異性中和抗體，這個結果表明接種季節性流 感疫苗可以誘導產生保護性的 B 細胞與抗體免疫反應。其中，個案 2023A 主要產 生譜系特異性中和抗體，而個案 2023B 主要產生交叉反應性中和抗體。此外，我 們將具有代表性的功能性抗體進行純化，進一步分析這些抗體對於近期和早期流行的 Victoria 譜系或是 Yamagata 譜系 B 型流感病毒的抗原辨識廣度和效度。我們 的研究結果表明大多數功能性抗體具有相當的抗原辨識廣度，能有效中和近期和 早期流行的病毒株。值得注意的是，交叉反應性中和抗體對 Yamagata 譜系病毒的 中和效力強。總言之，我們的研究深入剖析了成人接種季節性流感疫苗後所誘發 生成 B 細胞衍生之抗 B 型流感病毒 HA 抗體株譜，發現除了譜系病毒特異性中和 抗體反應外，尚有相當程度之跨譜系中和抗體反應生成。這些研究成果協助我們 進一步了解季節性流感疫苗觸發的免疫反應在對抗 B 型流感病毒所可能扮演的角 色，也有助於未來對於 B 型流感病毒 HA 抗原性的評估。

Influenza B viruses co-circulate with influenza A viruses and cause seasonal outbreaks around the world. Influenza virus contain two major surface proteins, hemagglutinin (HA) and neuraminidase. Based on antigenic difference of HA, influenza B virus is classified into two antigenically distinct lineages, Victoria and Yamagata lineages. Seasonal influenza vaccination is widely regarded as one effective method to elicit protective immune response against influenza and protection is mainly mediated by HA-reactive antibodies. However, human anti-influenza B HA B-cell and antibody responses after vaccination remain largely unclear. In the study, we constructed B cell-derived anti-influenza B HA antibody repertoires from two adult individuals upon immunization with 2022-2023 Northern Hemisphere quadrivalent influenza vaccine. We detected a broad range of anti-influenza B HA antibody response which is composed of Victoria lineage virus-specific, Yamagata lineage virus-specific and cross-reactive antibodies. Neutralizing antibodies that are specific to HA head domain of recent circulating Victoria or Yamagata lineage virus were identified, indicative of the elicitation of protective humoral immunity upon seasonal vaccination. Donor 2023A predominantly produced lineage-specific neutralizing antibodies, while donor 2023B primarily generated cross-reactive neutralizing antibodies. Furthermore, we used purified antibodies to delineate the antigenic breadth and potency of representative functional antibodies against recent and earlier circulating Victoria and Yamagata lineage influenza B viruses. Our results revealed that most functional antibodies exhibited broad antigenic breadth that effective neutralizing earlier circulating virus strains. Notably, cross-reactive neutralizing antibodies demonstrated a strong potency against Yamagata lineage viruses. In summary, out study delve into the details of B cell-derived anti-influenza B HA antibody repertoires elicited upon seasonal influenza vaccination in adults, not only observing lineage-specific neutralizing antibody responses, but also a significant degree of generating cross-reactive neutralizing antibodies. These results assist in our understanding of the role of vaccine immunogenicity in combating influenza B virus and contribute to future assessments of the antigenicity of influenza B virus HA.