EBioMedicine
·
2022
·
IF 11.205
Mengyi Zhang,Yimeng An,Xi Wu,Meina Cai,Xinyu Zhang,Chaoying Yang,Jincheng Tong,Zhimin Cui,Xueli Li,Weijin Huang,Chenyan Zhao,Youchun Wang
Summary Background Influenza A (H3N2) virus (A/H3N2) has complex antigenic evolution, resulting in frequent vaccine strain updates. We aimed to evaluate the protective effect of the vaccine strains on the circulating strains from past ten years and provide a basis for finding a broader and more efficient A/H3N2 vaccine strain. Methods Eighty-four representative circulating A/H3N2 strains were selected from 65,791 deposited sequences in 2011–2020 and pseudotyped viruses were constructed with the VSV vector. We immunized guinea pigs with DNA vaccine containing the A/H3N2 components of the vaccine strains from 2011 to 2021 and tested neutralizing antibody against the pseudotyped viruses. We used a hierarchical clustering method to classify the eighty-four representative strains into different antigenic clusters. We also immunized animals with monovalent vaccine stock of the vaccine strains for the 2020–2021 and 2021–2022 seasons and tested neutralizing antibody against the pseudotyped viruses. Findings The vaccine strains PE/09, VI/11 and TE/12 induced higher levels of neutralizing antibody against representative strains circulating in recommended year and the year immediately prior whereas vaccine strains HK/14, HK/19 and CA/20 induced poor neutralization against all representative strains. The representative strains were divided into five antigenic clusters (AgV), which were not identical to gene clades. The AgV5 strains were most difficult to be protected among the five clusters. Compared with single-dose immunization, three doses of monovalent vaccine stock (HK/19 or CA/20) could induce stronger and broader neutralizing antibodies against strains in each of the antigenic clusters. Interpretation The protective effect of vaccine strains indicated that the accurate selection of A/H3N2 vaccine strains must remain a top priority. By increasing the frequency of immunization, stronger and broader neutralizing antibodies against strains in all antigenic clusters were induced, which provides direction for a new immunization strategy. Funding This work was supported by a grant from National Key R&D Program of China (No. 2021YFC2301700 ).
研究领域:
病毒学
·
免疫学
·
流行病学
✓ 已验证
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2022
·Vol. 7
·期 1
·1-10
·
IF 38.104
Wu Jiajing,Nie Jianhui,Zhang Li,Song Hao,An Yimeng,Liang Ziteng,Yang Jing,Ding Ruxia,Liu Shuo,Li Qianqian,Li Tao,Cui Zhimin,Zhang Mengyi,He Peng,Wang Youchun,Qu Xiaowang,Hu Zhongyu,Wang Qihui,Huang Weijin
Emerging SARS-CoV-2 variants are the most serious problem for COVID-19 prophylaxis and treatment. To determine whether the SARS-CoV-2 vaccine strain should be updated following variant emergence like seasonal flu vaccine, the changed degree on antigenicity of SARS-CoV-2 variants and H3N2 flu vaccine strains was compared. The neutralization activities of Alpha, Beta and Gamma variants’ spike protein-immunized sera were analysed against the eight current epidemic variants and 20 possible variants combining the top 10 prevalent RBD mutations based on the Delta variant, which were constructed using pseudotyped viruses. Meanwhile, the neutralization activities of convalescent sera and current inactivated and recombinant protein vaccine-elicited sera were also examined against all possible Delta variants. Eight HA protein-expressing DNAs elicited-animal sera were also tested against eight pseudotyped viruses of H3N2 flu vaccine strains from 2011–2019. Our results indicate that the antigenicity changes of possible Delta variants were mostly within four folds, whereas the antigenicity changes among different H3N2 vaccine strains were approximately 10–100-fold. Structural analysis of the antigenic characterization of the SARS-CoV-2 and H3N2 mutations supports the neutralization results. This study indicates that the antigenicity changes of the current SARS-CoV-2 may not be sufficient to require replacement of the current vaccine strain.
研究领域:
病毒学
·
免疫学
·
流行病学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Xiaotong Wang,Tongtong Ye,Shaohui Geng,Shuna Ren,Xuming Zhao,Lihua Chen
A dual-signal strategy was developed based on a coordination reaction between iron(II) ions (Fe 2+ ) and potassium hexacyanoferrate(III) (K 3 [Fe(CN) 6 ]) to distinguish between brucella vaccine and wild strain. Utilizing metal-organic frameworks (MOFs), MOF Al (aluminum) @Fe 2+ @P 1 and MOF Fe @P 2 were synthesized and affixed to a hyaluronic acid (HA)-doped electrode. Hairpin probe 1 (P 1 ) has a common sequence (P 1 ') recognizing a fragment (T 1 ) in vaccines and wild strains. In contrast, hairpin probe 2 (P 2 ) has a differential sequence (P 2 ') only targeting a specific fragment (T 2 ) in the wild strain. Experimental findings indicated that activation of T 1 led to the dissociation of P 1 from MOF Al @Fe 2+ @P 1 , which released Fe 2+ into a buffer containing trace Fe 2+ . Following this, the addition of hydrogen peroxide (H 2 O 2 ) and K 3 [Fe(CN) 6 ] resulted in the formation of KFe[Fe(CN) 6 ] (PB). In contrast, specific activation of T 2 caused the detachment of P 2 from MOF Fe , thereby exposing its catalytic site. In H 2 O 2 , this catalytic site facilitated the conversion of trace Fe 2+ in buffer to Fe 3+ , with no PB generated after the addition of K 3 [Fe(CN) 6 ]. Simultaneous activation of T 1 and T 2 promoted the oxidation of Fe 2+ released from MOF Al by the exposed catalytic site of MOF Fe . The ratio of K 3 [Fe(CN) 6 ] to PB exhibited dynamic changes. Specifically, the ratio below 2.37 ± 0.05 indicated a Brucella-positive sample, whereas a ratio under 0.9 ± 0.02 suggested a sample derived from the vaccine. The scarcity of dual-signal sensors employing coordination reactions underscores the significance of this approach. Moreover, it addressed the challenges associated with brucella detection, demonstrating robust analytical performance.
研究领域:
生物化学
·
医学检测
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
ANALYST
·
2024
·
IF 3.6
Dong Li,Shuna Ren,Xiaotong Wang,Lili Chen,Shuang You,Yan Tang,Lihua Chen
In the assay for Brucella, the identification and differentiation of wild strains and vaccine strains present a significant challenge. Currently, there aren't any commercially available product to address this issue. In this study, we have developed a novel gated nanoprobe by utilizing Metal–Organic Frameworks (MOFs) as a scaffold and hairpin DNA as a “gating switch”. Specifically, Probe 1 with hairpin structure (P1h) targets a gene that is present in both wild strains Y3 (B. melitensis biovar 3) and vaccine strains A19 (Brucella abortus strains A19). We successfully applied this probe to screen positive samples of Brucella without any cross-reactivity with other substances. Additionally, we identified another specific gene exclusively found in wild strains, which serves as Probe 2 with hairpin structure (P2h) to confirm the strain type. Simultaneous detachment of both P1h and P2h from the MOFs leads to the release of Rhodamine 6G (Rho 6G) and Fluorescein (Flu), specifically indicating the presence of wild strains. If only P1h detaches and the Flu signal is detected, it suggests the presence of vaccine strains. Importantly, this method offers high accuracy, with a detection rate of 90% and a recovery rate of 94.71% to 107.65%, while avoiding cross-reactions with MO and TB. This one-step experiment provides reliable identification and differentiation of Y3 and A19, addressing concerns related to long periodicity, interference from individual variations, and the complex design of primers in existing laboratory methods. Furthermore, our approach successfully detects target 1 (T1) and target 2 (T2) at concentrations ranging from 10−6 M to 10−9 M, with a detection limit of 6.7 × 10−10 M and 6.4 × 10−10 M, respectively. Importantly, our strategy is cost-effective (around $1) and offers higher detection efficiency compared to traditional laboratory methods.
研究领域:
微生物学
·
纳米技术
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）