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Universal influenza virus vaccines: what can we learn from the human immune response following exposure

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 471-479 doi: 10.1007/s11684-017-0602-z

摘要：

Several universal influenza virus vaccine candidates based on eliciting antibodies against the hemagglutinin stalk domain are in development. Typically, these vaccines induce responses that target group 1 or group 2 hemagglutinins with little to no cross-group reactivity and protection. Similarly, the majority of human anti-stalk monoclonal antibodies that have been isolated are directed against group 1 or group 2 hemagglutinins with very few that bind to hemagglutinins of both groups. Here we review what is known about the human humoral immune response to vaccination and infection with H7 subtype influenza viruses on a polyclonal and monoclonal level. It seems that unlike vaccination with H5 hemagglutinin, which induces antibody responses mostly restricted to the group 1 stalk domain, H7 exposure induces both group 2 and cross-group antibody responses. A better understanding of this phenomenon and the underlying mechanisms might help to develop future universal influenza virus vaccine candidates.

关键词： universal influenza virus vaccine     hemagglutinin stalk     H7N9    

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Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in

Yulu Wang, Dan Hu, Yanling Wu, Tianlei Ying

《医学前沿（英文）》 2020年 第14卷 第2期   页码 149-159 doi: 10.1007/s11684-020-0764-y

摘要： Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates. Despite significant efforts to address influenza, it remains a major threat to human public health. This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants. Moreover, designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult. Some novel epitopes hidden in the hemagglutinin (HA) trimeric interface have been discovered recently, and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates. These findings may have important implications for the development of universal influenza vaccines and antiviral drugs. In this review, we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.

关键词： influenza virus     neutralizing antibody     hemagglutinin     globular head region     trimeric interface    

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Avian influenza A: an avian influenza virus from low pathogenic to highly pathogenic

William J. Liu, Haixia Xiao, Lianpan Dai, Di Liu, Jianjun Chen, Xiaopeng Qi, Yuhai Bi, Yi Shi, George F. Gao, Yingxia Liu

《医学前沿（英文）》 2021年 第15卷 第4期   页码 507-527 doi: 10.1007/s11684-020-0814-5

摘要： The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

关键词： H7N9     HPAIV     epidemiology     clinical features     pathogenesis     hemagglutinin     immunity     vaccine    

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Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection:implications in vaccine design

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《医学前沿（英文）》 2017年 第11卷 第4期   页码 480-489 doi: 10.1007/s11684-017-0594-8

摘要：

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

关键词： human immunodeficiency virus type I     superinfection     incidence     immune response    

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Assessment of vaccination strategies against highly pathogenic avian influenza in China

Honglei SUN,Jinhua LIU

《农业科学与工程前沿（英文）》 2014年 第1卷 第4期   页码 277-281 doi: 10.15302/J-FASE-2014036

摘要： Vaccination for highly pathogenic avian influenza (HPAI) has been implemented in China for a decade, however, the virus is still present in poultry. A series of recombinant vaccines, Re-1 to Re-7, have been developed and used, and Re-8 will also be used in clinical settings to prevent the prevailing flu strains. The question remains, when can China eradicate the disease? Here, we review the epidemiology of H5 HPAI along with the development, usage and problems of vaccines. Further suggestions for controlling the disease in China are provided.

关键词： highly pathogenic avian influenza     vaccine     vaccination     control    

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Seroprevalence of influenza viruses in Shandong, Northern China during the COVID-19 pandemic

《医学前沿（英文）》 2022年 第16卷 第6期   页码 984-990 doi: 10.1007/s11684-022-0930-5

摘要： Nonpharmaceutical interventions (NPIs) have been commonly deployed to prevent and control the spread of the coronavirus disease 2019 (COVID-19), resulting in a worldwide decline in influenza prevalence. However, the influenza risk in China warrants cautious assessment. We conducted a cross-sectional, sero-epidemiological study in Shandong Province, Northern China in mid-2021. Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains. A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic. The overall seroprevalence values against A/H1N1pdm09, A/H3N2, B/Victoria, and B/Yamagata were 17.8% (95% CI 16.2%–19.5%), 23.5% (95% CI 21.7%–25.4%), 7.6% (95% CI 6.6%–8.7%), and 15.0 (95% CI 13.5%–16.5%), respectively, in the study period. The overall vaccination rate was extremely low (2.6%). Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals (P < 0.001). Notably, the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic ( P < 0.01). Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

关键词： influenza virus     seroprevalence     antibody     COVID-19     cross-sectional study    

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Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

Kelvin Kai-Wang TO FRCPath, Iris Wai-Sum LI FRCP, Ivan Fan-Ngai HUNG FRCP, Vincent Chi-Chung CHENG FRCPath, Kwok-Yung YUEN MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 147-156 doi: 10.1007/s11684-010-0030-9

摘要： The pandemic H1N1 2009 influenza virus has caused the first influenza pandemic of the 21st century, leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the illness. Advances in sci

关键词： influenza A virus     H1N1 subtype     pandemic     pathogenesis     virulence factors     immunity     management     antiviral    

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Research progress on human infection with avian influenza H7N9

Xiaoxin Wu, Lanlan Xiao, Lanjuan Li

《医学前沿（英文）》 2020年 第14卷 第1期   页码 8-20 doi: 10.1007/s11684-020-0739-z

摘要： Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. Meanwhile, the H7N9 virus continues to accumulate mutations, and its affinity for the human respiratory epithelial sialic acid 2-6 receptor has increased. Therefore, a pandemic is still possible. In the past 6 years, we have accumulated rich experience in dealing with H7N9, especially in terms of virus tracing, epidemiological research, key site mutation monitoring, critical disease mechanisms, clinical treatment, and vaccine development. In the research fields above, significant progress has been made to effectively control the spread of the epidemic and reduce the fatality rate. To fully document the research progress concerning H7N9, we reviewed the clinical and epidemiological characteristics of H7N9, the key gene mutations of the virus, and H7N9 vaccine, thus providing a scientific basis for further monitoring and prevention of H7N9 influenza epidemics.

关键词： H7N9     pandemic     epidemiology     mutations     vaccine     influenza    

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Research and development of a novel subunit vaccine for the currently circulating pseudorabies virus

Yuzhou WANG,Tongyan WANG,He YAN,Fanli YANG,Linghua GUO,Qingyuan YANG,Xule HU,Feifei TAN,Yan XIAO,Xiangdong LI,Kegong TIAN

《农业科学与工程前沿（英文）》 2015年 第2卷 第3期   页码 216-222 doi: 10.15302/J-FASE-2015072

摘要： Pseudorabies (PR) is a devastating viral disease which leads to fatal encephalitis and respiratory disorders in pigs. Commercial gE-deleted live pseudorabies virus (PRV) vaccine has been widely used to control this disease in China. However, the new-emerging variants of PRV compromises the protection provided by current vaccines and lead to the outbreak of PR in vaccinated pig herds. Several killed and live vaccine candidates based on current PRV variants have been reported to be effective to control the disease. A subunit vaccine based on gB protein, one major PRV glycoprotein which elicits strong humoral and cellular immune responses, however, was never evaluated for protection against the current circulating PRV variants. In this study, full-length PRV gB protein was successfully expressed in baculovirus/insect cells in the soluble format and was tested on 3-week-old piglets as a subunit vaccine. Compared with unvaccinated pigs, the gB-vaccinated pigs developed specific antibody-mediated responses and were protected from the virulent PRV HN1201 challenge. All vaccinated pigs survived without showing any PRV-specific respiratory and neurological signs, but all unvaccinated pigs died within 7 days after HN1201 challenge. Hence, this novel gB-based vaccine could be applied as an effective subunit vaccine to control PRV variant in China.

关键词： pseudorabies virus     glycoprotein B protein     subunit vaccine    

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Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine

Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 390-395 doi: 10.1007/s11684-009-0087-5

摘要： We constructed a eukaryotic expression plasmid encoding Epstein-Barr virus latent membrane protein 2 (EBV, LMP2) and evaluated its effects on humoral immunity. First, the encoding sequence of the EBV was amplified from B95−8 cell RNA by reverse transcription polymerase chain reaction (RT-PCR) and then was directionally cloned into eukaryotic expression vector pcDNA3.1. It was employed to evaluate immune response of the mice inoculated doubly with the DNA vaccine. The serum antibody against LMP2 was detected with enzyme-linked immunosorbent assay (ELISA). The recombinant plasmid pcDNA3.1- was confirmed by the restrictive endonuclease analysis and sequence analysis. The serum titer of IgG antibody against LMP2 epitope in the mice immunized with the DNA vaccine encoding LMP2 was up to 1∶4000. In conclusion, the EBV DNA vaccine can induce a strong humoral immune response in mice.

关键词： Epstein-Barr virus     latent membrane protein 2     nasopharyngeal carcinoma     humoral immunity    

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i>RR1 and RR2 gene deletion affects the immunogenicity of a live attenuated pseudorabies virusvaccine candidate in natural pig host

Shijun YAN,He YAN,Chaolin ZHANG,Tongyan WANG,Qingyuan YANG,Zhe SUN,Yan XIAO,Feifei TAN,Xiangdong LI,Kegong TIAN

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 81-86 doi: 10.15302/J-FASE-2016088

摘要： As virulence-determining genes, and encode the small subunit and large subunit of viral ribonucleotide reductase (RR) in pseudorabies virus which have been extensively studied in mice. However, their role in pigs has not been adequately investigated. In this study, we deleted and genes based on a / / triple gene-deleted pseudorabies virus and tested its efficacy in pigs as a vaccine candidate. The rescued virus showed similar growth properties and plaque size as its parent strain. In an animal study, the virus could elicit humoral immune responses shown by generation of gB-specific antibodies and virus neutralizing antibodies. However, vaccination could not provide protection against virulent pseudorabies virus challenge since vaccinated pigs showed clinical pseudorabies-specific syndromes. The deficiency in protection may due to the generation of late and low levels of gB antibodies and virus neutralizing antibodies.

关键词： pseudorabies virus     RR1 and RR2     ribonucleotide reductase     vaccine candidate    

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Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry

Jiao HU,Xiufan LIU

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 11-24 doi: 10.15302/J-FASE-2016092

摘要： The H9N2 and H5N1 avian influenza viruses (AIVs) have been circulating in poultry in China and become endemic since 1998 and 2004, respectively. Currently, they are prevalent in poultry throughout China. This endemicity makes them actively involved in the emergence of the novel lineages of other subtypes of influenza viruses, such as the well-known viruses of the highly pathogenic avian influenza (HPAI) H5N2 and the 2013 novel H7N7, H7N9 and H10N8 subtypes, thereby threatening both the poultry industry and public health. Here, we will review briefly the prevalence and evolution, pathogenicity, transmission, and disease control of these two subtypes and also discuss the possibility of emergence of potentially virulent and highly transmissible AIVs to humans.

关键词： avian influenza virus     H9N2     H5N1     novel viruses     public health    

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The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

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《医学前沿（英文）》 2013年 第7卷 第3期   页码 333-344 doi: 10.1007/s11684-013-0275-1

摘要：

This study reports the first death caused by a novel avian influenza A (H7N9) virus in Zhejiang Province, China. The patient had chronic hepatitis B and history of exposure to poultry. The patient initially complained of diarrhea and influenza-like symptoms on March 7 and 14 respectively. The disease progressed to severe pneumonia, sustained hypoxia, and coagulation abnormalities. The patient died on March 27 because of respiratory failure, multiple organ failure, and disseminated intravascular coagulation without oseltamivir treatment. This H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai, Jiangsu, Anhui, etc. Analysis of hemagglutinin, neuramidinase, and matrix genes indicated that the isolates share the same avian origin, have low virulence, and are sensitive to oseltamivir, but are resistant to adamantine. Only the isolate that caused the fatality exhibited substitution of Q226I in the HA gene, which indicates a potentially enhanced human affinity. The secondary transmission rate was 1.6% (2/125). Only two health workers presented with influenza-like symptoms, and they subsequently tested negative for H7N9 RNA. In conclusion, underlying disease, late diagnosis, and untimely antiviral treatment are possible high-risk factors for infections and death caused by the low-pathogenicity avian influenza A (H7N9). Person-to-person transmission of the H7N9 virus was not detected among close contacts, but such transmission should be investigated in the future. Expanding and enhancing surveillance will help in the early discovery and diagnosis of suspected cases, which will reduce the number of severe cases and deaths.

关键词： avian influenza A (H7N9) virus     epidemiology     contacts     person-to-person transmission    

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从H1N1血凝素序列提取的沙门氏菌传递的COBRA-HA1抗原对甲型流感亚型产生广谱保护作用 Article

Ram Prasad Aganja, Amal Senevirathne, Chandran Sivasankar, John Hwa Lee

《工程（英文）》 2024年 第32卷 第1期   页码 42-57 doi: 10.1016/j.eng.2023.08.001

摘要：

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutinin globular head portion (HA1) of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs. Constructs carrying different HA1 regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RdRp-dependent eukaryotic expression system, pJHL204. Recombinant protein expression was confirmed by Western blot and immunofluorescence assays. Mice immunized with the designed constructs produced a humoral response, with a significant increase in immunoglobulin G (IgG) levels, and a cell-mediated immune response, including a 1.5-fold increase in CD4+ and CD8+ T cells. Specifically, constructs #1 and #5 increased the production of interferon-γ (IFN-γ) producing CD4+ and CD8+ T cells, skewing the response toward the T helper type 1 cell (Th1) pathway. Additionally, interleukin-4 (IL-4)-producing T cells were upregulated 4-fold. Protective efficacy was demonstrated, with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer > 40 against the selected viral strains. The designed constructs conferred a broadly protective immune response, resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34, A/Brisbane/59/2007, A/California/07/2009, KBPV VR-92, and NCCP 43021 strains. This discovery revolutionizes influenza vaccine design and delivery; Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy. This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.

关键词： COBRA     Influenza A     Salmonella     Vaccine     Broad spectral protection    

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Innovation-driven trend shaping COVID-19 vaccine development in China

《医学前沿（英文）》 doi: 10.1007/s11684-023-1034-6

摘要： Confronted with the coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

关键词： SARS-CoV-2     COVID-19 vaccine     vaccine development    

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标题 作者 时间 类型 操作

Universal influenza virus vaccines: what can we learn from the human immune response following exposure

null

期刊论文

Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in

Yulu Wang, Dan Hu, Yanling Wu, Tianlei Ying

期刊论文

Avian influenza A: an avian influenza virus from low pathogenic to highly pathogenic

William J. Liu, Haixia Xiao, Lianpan Dai, Di Liu, Jianjun Chen, Xiaopeng Qi, Yuhai Bi, Yi Shi, George F. Gao, Yingxia Liu

期刊论文

Immunological and virological characteristics of human immunodeficiency virus type 1 superinfection:implications in vaccine design

null

期刊论文

Assessment of vaccination strategies against highly pathogenic avian influenza in China

Honglei SUN,Jinhua LIU

期刊论文

Seroprevalence of influenza viruses in Shandong, Northern China during the COVID-19 pandemic

期刊论文

Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

Kelvin Kai-Wang TO FRCPath, Iris Wai-Sum LI FRCP, Ivan Fan-Ngai HUNG FRCP, Vincent Chi-Chung CHENG FRCPath, Kwok-Yung YUEN MD,

期刊论文

Research progress on human infection with avian influenza H7N9

Xiaoxin Wu, Lanlan Xiao, Lanjuan Li

期刊论文

Research and development of a novel subunit vaccine for the currently circulating pseudorabies virus

Yuzhou WANG,Tongyan WANG,He YAN,Fanli YANG,Linghua GUO,Qingyuan YANG,Xule HU,Feifei TAN,Yan XIAO,Xiangdong LI,Kegong TIAN

期刊论文

Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine

Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,

期刊论文

i>RR1 and RR2 gene deletion affects the immunogenicity of a live attenuated pseudorabies virusvaccine candidate in natural pig host

Shijun YAN,He YAN,Chaolin ZHANG,Tongyan WANG,Qingyuan YANG,Zhe SUN,Yan XIAO,Feifei TAN,Xiangdong LI,Kegong TIAN

期刊论文

Endemicity of H9N2 and H5N1 avian influenza viruses in poultry in China poses a serious threat to poultry

Jiao HU,Xiufan LIU

期刊论文

The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

null

期刊论文

从H1N1血凝素序列提取的沙门氏菌传递的COBRA-HA1抗原对甲型流感亚型产生广谱保护作用

Ram Prasad Aganja, Amal Senevirathne, Chandran Sivasankar, John Hwa Lee

期刊论文

Innovation-driven trend shaping COVID-19 vaccine development in China

期刊论文