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PubMed2025

Bacteriophages as vaccine platforms: Opportunities and challenges in translation.

Bacteriophages (phages) have recently received increased interest as versatile candidates for vaccine development. Their inherent characteristics, such as ease of genetic manipulation, high-density antigen display, intrinsic immunostimulatory properties, demonstrated human safety, and scalability in bacterial hosts, make them attractive as next-generation vaccine platforms. Additionally, their cost-effective production, stability, and existing regulatory approval for food and compassionate phage therapy provide a strong foundation for further development of phage-based vaccines. This commentary summarizes the types of phages, the strategies used, and current advances in phage-based vaccine development for viral and bacterial targets, and discusses the promises and challenges of this platform for novel vaccine development. Phage-based vaccines represent an innovative and promising platform for vaccine development to address significant medical and public health challenges, particularly in antimicrobial resistance, pandemic preparedness, and One Health. Accumulative experimental data have demonstrated that phage-based vaccines induce specific cellular, humoral, and mucosal immune responses at magnitudes comparable to those induced by other vaccine platforms. However, a better understanding of phage biology (interactions with the human immune system and microbiome), more carefully designed preclinical studies, Good Manufacturing Practice production development, the regulatory framework, and ultimately clinical trials are needed before the full potential of this platform is realized.

Animals↗

PubMed2001

Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function.

Induction of heterosubtypic immunity to influenza viral antigens is of paramount importance to the prevention of epidemics and potential pandemics. The 1997 incidence of avian influenza infections in humans in Hong Kong heightened the need for pandemic preparedness and a search for vaccines and vaccine delivery systems that can confer broad protection. In this report, we demonstrate that the delivery of H1N1 subtype influenza viral antigens as immunostimulating complexes (ISCOM) induces broad cross-protection in mice against challenge with various influenza virus subtypes, including the avian H9 and the H5 strains that were recently responsible for deaths in humans. The ISCOM delivery system induced high and long-lived serum antiviral antibodies and class I-restricted cytotoxic T-lymphocytes (CTL). Studies with perforin, IFN-gamma, and mu-chain gene knock-out mice demonstrated that the heterosubtypic protection required cross-reactive, functional cytotoxic T cells and nonhemagglutination inhibiting serum antibodies. Interferon-gamma, a major player in viral clearance by nonlytic mechanisms, did not appear to play a role in heterosubtypic immunity. Nonformulated H1N1 influenza antigens failed to induce significant CTL or long-lasting antibody responses or to protect mice against challenge with heterosubtypic viruses. Furthermore, while influenza virus infection induced a dominant nucleoprotein (NP)-specific CTL response in H2 mice, the ISCOM delivery system induced a dominant hemagglutinin-specific CTL response. Moreover, non-neutralizing but cross-reactive antibodies played a role in reducing viral titers by macrophages. These results suggest that exogenous delivery of influenza antigens as ISCOM can influence their antigen processing and presentation, their ability to induce/recall CTL specificities, and their capacity to mediate broad cross-protection against influenza virus variants.

Animals↗

PubMed2002

H5N1 influenza viruses isolated from geese in Southeastern China: evidence for genetic reassortment and interspecies transmission to ducks.

The H5N1 viruses (H5N1/97) associated with the "bird-flu" incident in the Hong Kong SAR have not been isolated since the slaughter of poultry in December 1997 brought that outbreak to an end. Recent evidence points to this virus as having arisen through a reassortment of a number of precursor avian viruses and a virus related to Goose/Guangdong/1/96 (H5N1) (Gs/Gd/96) was the likely donor of the H5 hemagglutinin. We characterize the Goose/Guangdong/1/96-like viruses isolated from geese and ducks imported into Hong Kong in the year 2000. Antigenically and genetically, these recent H5N1 viruses fall into two groups, one mainly associated with geese, and the other, recently transmitted to ducks. Further, viruses isolated from a goose and a duck in December 2000 have acquired NS, PA, M, and PB2 genes from the aquatic avian influenza gene pool through reassortment. For pandemic preparedness, it is important to monitor whether these reassortant viruses have the capacity for interspecies transmission to terrestrial poultry or mammals.

Animals↗

PubMed2000

Virologic and serologic surveillance for human, swine and avian influenza virus infections among pigs in the north-central United States.

Influenza virus infection in pigs is both an animal health problem and a public health concern. As such, surveillance and characterization of influenza viruses in swine is important to the veterinary community and should be a part of human pandemic preparedness planning. Studies in 1976/1977 and 1988/1989 demonstrated that pigs in the U.S. were commonly infected with classical swine H1N1 viruses, whereas human H3 and avian influenza virus infections were very rare. In contrast, human H3 and avian H1 viruses have been isolated frequently from pigs in Europe and Asia over the last two decades. From September 1997 through August 1998, we isolated 26 influenza viruses from pigs in the north central United States at the point of slaughter. All 26 isolates were H1N1 viruses, and phylogenetic analyses of the hemagglutinin and nucleoprotein genes from 11 representative viruses demonstrated that these were classical swine H1 viruses. However, monoclonal antibody analyses revealed antigenic heterogeneity among the HA proteins of the 26 viruses. Serologically, 27.7% of 2,375 pigs tested had hemagglutination-inhibiting antibodies against classical swine H1 influenza virus. Of particular significance, however, the rates of seropositivity to avian H1 (7.6%) and human H3 (8.0%) viruses were substantially higher than in previous studies.

Amino Acid Sequence↗

PubMed2005

Implementation of the community network of reference laboratories for human influenza in Europe.

BACKGROUND: The increased need for accurate influenza laboratory surveillance data in the European Union required formalisation of the existing network of collaborating national influenza reference laboratories participating in the European Influenza Surveillance Scheme (EISS). OBJECTIVE: To establish a Community Network of Reference Laboratories for Human Influenza in Europe (CNRL). METHODS: Virologists in EISS defined the objective and tasks of the CNRL. Performance of the laboratories in the tasks was monitored by questionnaire-based inventories and quality control assessments (QCA). Subsequently, actions were defined to improve the performance of the CNRL. RESULTS: The CNRL started in April 2003 and included as of May 2004 32 laboratories in 24 European countries. The objective is to provide high quality reference services for human influenza surveillance, early warning and pandemic preparedness in Europe. The defined basic tasks are direct detection, culture, typing, subtyping and strain characterisation of influenza virus, diagnostic influenza serology and storage of clinical specimens and virus isolates. The questionnaire-based inventories and QCAs revealed that the majority of CNRL laboratories perform well in most of the basic tasks, although improvements are needed in certain areas of virus testing. Therefore, task groups have been established to further improve the methods used in the network. The CNRL has proven its usefulness during the 2003-2004 season by the reporting of accurate data concerning the flu epidemic caused by A/Fujian/411/2002 (H3N2)-like viruses and by the rapid sharing of information, protocols and reagents during the A(H5N1) and A(H7N3) epizootics in Asia and Canada. CONCLUSION: EISS has established a functioning Community Network of Reference Laboratories for Human Influenza in Europe and laid the foundation for further enhancement and collaborations. Important next steps include improving the laboratories to carry out all basic tasks and collaboration with the European Centre for Disease Prevention and Control.

Community Networks↗

PubMed2005

The virosome concept for influenza vaccines.

There is a need for more efficacious inactivated influenza vaccines, since current formulations show suboptimal immunogenicity in at-risk populations, like the elderly. More effective vaccines are also urgently needed for an improved influenza pandemic preparedness. In this context, there is considerable interest in virosomes. Virosomes are virus-like particles, consisting of reconstituted influenza virus envelopes, lacking the genetic material of the native virus. Virosomes are produced from influenza virus through a detergent solubilization and removal procedure. Properly reconstituted virosomes retain the cell binding and membrane fusion properties of the native virus, mediated by the viral envelope glycoprotein haemagglutinin. These functional characteristics of virosomes form the basis for their enhanced immunogenicity. First, the repetitive arrangement of haemagglutinin molecules on the virosomal surface mediates a cooperative interaction of the antigen with Ig receptors on B lymphocytes, stimulating strong antibody responses. In addition, virosomes interact efficiently with antigen-presenting cells, such as dendritic cells, resulting in activation of T lymphocytes. In a murine model system, virosomes, as compared to conventional subunit vaccine, which consists of isolated influenza envelope glycoproteins, induce a more balanced T helper 1 versus T helper 2 response, virosomes in particular eliciting stronger T helper 1 responses than subunit vaccine. Also, as a result of fusion of the virosomes with the endosomal membrane, part of the virosomal antigen gains access to the major histocompatibility class I presentation pathway, thus priming cytotoxic T lymphocyte activity. Finally, virosomes represent an excellent platform for inclusion of lipophilic adjuvants for further stimulation of vaccine immunogenicity. By virtue of these characteristics, virosomes represent a promising novel class of inactivated influenza vaccines, which not only induce high virus-neutralizing antibody titres, but also prime the cellular arm of the immune system.

Antigen Presentation↗

PubMed2006

Epidemic and pandemic influenza, who cares and how?

The 2005 hurricanes, Katrina and Rita, demonstrated that Mother Nature remains a bigger threat to mankind than bioterrorism or even terrorism. This is no less the case in the expected influenza pandemic that could infect up to 1 billion people worldwide killing millions and disrupting the supply of essential services and provoking social disruption. With influenza however, mankind does have the opportunity to make necessary preparations for the threat of a pandemic that could break out tomorrow, next year or within the next decade. Indeed, the events in New Orleans have sent "a strong message that knowledge is not enough, everyone predicted it [referring to hurricane Katrina], but no one did much about it--you need a detailed plan to deal with these threats," explained Dr. J.S. Oxford to the conference seminar on "epidemic and pandemic influenza, who cares and how?" During this session, participants discussed the state of pandemic preparedness listening to representatives from the UK and Canada who presented overviews of their preparedness plans, viewed as among the best examples of current practice and to a study on compliance with the WHO guidelines on flu vaccination.

Antiviral Agents↗

PubMed2005

Evolution of H9N2 influenza viruses from domestic poultry in Mainland China.

H9N2 viruses have circulated in domestic poultry in Mainland China since 1994, and an inactivated vaccine has been used in chickens to control the disease since 1998. The present study analyzed 27 H9N2 avian influenza viruses that were isolated from chickens and ducks from 1996 to 2002. Infection studies indicated that most of the viruses replicate efficiently but none of them is lethal for SPF chickens. However, these viruses exhibit different phenotypes of replication in a mouse model. Five viruses, including 4 early isolates and one 2000 isolate, are not able to replicate in mice; 14 viruses replicate to moderate titers in mouse lungs and cause less than 5% weight loss, while other 8 viruses could replicate to high titers in the lungs and 7 of them induce 10-20% weight loss of the mice on day 5 after inoculation. Most of the viruses isolated after 1996 are antigenically different from the vaccine strain that is currently used in China. Three viruses isolated in central China in 1998 are resistant to adamantanes. Phylogenetic analysis revealed that all of the viruses originated from CK/BJ/1/94-like virus and formed multiple genotypes through complicated reassortment with QA/HK/G1/97-, CK/HK/G9/97-, CK/SH/F/98-, and TY/WI/66-like viruses. This study is a description of the previously uncharacterized H9N2 avian influenza viruses recently circulating in chickens and ducks in Mainland China. Our findings suggest that urgent attention should be paid to the control of H9N2 influenza viruses in animals and to the human's influenza pandemic preparedness.

Animals↗

PubMed2001

Characterization of a human H9N2 influenza virus isolated in Hong Kong.

Two H9N2 viruses were isolated, for the first time, from humans in Hong Kong in 1999. Isolation of influenza viruses with a novel subtype of the hemagglutinin (HA) drew attention of health care authorities worldwide from the view of pandemic preparedness. Sequence analysis of the HA genes reveals that HA of A/Hong Kong/1073/99 (H9N2) is most closely related to that of A/quail/HK/G1/97 (H9N2) that contains the internal genes similar to those of Hong Kong/97 (H5N1) viruses. Phylogenetic and antigenic analyses demonstrated the diversity among H9 HA. A/Hong Kong/1073/99 was shown to cause a respiratory infection in Syrian hamsters, suggesting that the virus can replicate efficiently in mammalian hosts. We developed a whole virion test vaccine with a formalin-inactivated egg-grown HK1073. Intraperitoneal administration of the vaccine twice to hamsters conferred a complete protection against challenge infection by the MDCK cell-grown homologous virus. Receptor specificity of HK1073 appeared different from that of other avian influenza viruses of H9 subtype which recognize preferentially alpha-2,3 linked sialic acid. Hemagglutination of HK1073 with guinea pig erythrocytes was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing polymers. These data suggested that HK1073 had acquired a broader host range, including humans. Together with data so far available, the present study suggested that isolation of the H9 influenza viruses from humans requires precaution against the emergence of a novel human influenza.

Animals↗

PubMed2003

The global agenda on influenza surveillance and control.

In collaboration with its many partners, WHO has developed a new Global Agenda on Influenza Surveillance and Control. The Global Agenda defines 17 priority activities that are critical to reducing the morbidity and mortality from annual influenza epidemics and preparing for the next pandemic. The Global Agenda will provide the foundation for global and national intervention plans, facilitate international coordination of prevention and control activities and contribute to renewed interest in epidemic influenza prevention and pandemic preparedness.

Global Health↗

PubMedDate not supplied

Human influenza virus A/HongKong/156/97 (H5N1) infection.

Introduction of influenza viruses with gene segments of avian origin into the human population may result in the emergence of new pathogenic human influenza viruses. The recent infection of a 3-year-old boy with an influenza A (H5N1) virus of avian origin can be considered as an example of such an event. However, this virus, influenza A/Hong Kong/156/97 (H5N1) and the 17 additional H5N1 viruses isolated from humans by the end of 1997 lack the ability to spread efficiently amongst humans and therefore have limited pandemic potential. However, the possibility of reassortment of these viruses with currently circulating human viruses illustrates the need for pandemic preparedness.

Animals↗

PubMed2000

Interspecies transmission of influenza viruses: H5N1 virus and a Hong Kong SAR perspective.

This account takes stock of events and involvements, particularly on the avian side of the influenza H5N1 'bird flu' incident in Hong Kong SAR in 1997. It highlights the role of the chicken in the many live poultry markets as the source of the virus for humans. The slaughter of chicken and other poultry across the SAR seemingly averted an influenza pandemic. This perspective from Hong Kong SAR marks the coming-of-age of acceptance of the role of avian hosts as a source of pandemic human influenza viruses and offers the prospect of providing a good baseline for influenza pandemic preparedness in the future. Improved surveillance is the key. This is illustrated through the H9N2 virus which appears to have provided the 'replicating' genes for the H5N1 virus and which has since been isolated in the SAR from poultry, pigs and humans highlighting its propensity for interspecies transmission.

Animals↗

PubMed2003

Phylogenetic analysis of hemagglutinin and neuraminidase genes of H9N2 viruses isolated from migratory ducks.

Genetic analysis indicated that the pandemic influenza strains derived from wild aquatic birds harbor viruses of 15 hemagglutinin (HA) and 9 neuraminidase (NA) antigenic subtypes. Surveillance studies have shown that H9N2 subtype viruses are worldwide in domestic poultry and could infect mammalian species, including humans. Here, we genetically analyzed the HA and NA genes of five H9N2 viruses isolated from the migratory ducks in Hokkaido, Japan, the flyway of migration from Siberia during 1997-2000. The results showed that HA and NA genes of these viruses belong to the same lineages, respectively. Compared with those of A/quail/Hong Kong/G1/97-like and A/duck/Hong Kong/Y280/97-like viruses, HA and NA of the migratory duck isolates had a close relationship with those of H9N2 viruses isolated from the chicken in Korea, indicating that the Korea H9N2 viruses might be derived from the migratory ducks. The NA genes of the five isolates were located in the same cluster as those of N2 viruses, which had caused a human pandemic in 1968, indicating that the NA genes of the previous pandemic strains are still circulating in waterfowl reservoirs. The present results further emphasize the importance of carrying out molecular epidemiological surveillance of H9N2 viruses in wild ducks to obtain more information for the future human influenza pandemics preparedness.

Amino Acid Sequence↗

PubMed2006

[Surveillance of acute respiratory illnesses (ARI) in Lower Saxony: first experience from the years 2005-2006].

In the context of influenza pandemic preparedness planning, a surveillance system for influenza and other acute respiratory illnesses was implemented in Lower Saxony at the beginning of the influenza season 2004/2005 and coordinated by the Governmental Institute of Public Health of Lower Saxony. This surveillance system represents an addition to already existing national monitoring systems. The goal of this surveillance system is to have available prompt information on the beginning, course and end of the influenza season and to recognise the spectrum of pathogens and identify outbreaks of other viral acute respiratory illnesses (ARI). For this purpose an all-season surveillance was established consisting of two supplementary modules. The first module is a symptom-oriented surveillance of acute respiratory illnesses in children of pre-school day care facilities. In the second module a virological surveillance in co-operation with selected medical practices was established. While the temporal course and burden of ARI in all Lower Saxony can be assessed by the surveillance of children in the day-care facilities in a sensitive, but less specific way, the virological surveillance provides highly specific information on the prevailing pathogens in ARI patients at a certain time. This information, in return, gives an indication about the responsible pathogens causing ARI in children of the day-care facilities. The first experience with these two complementary surveillance modules shows that in Lower Saxony a well accepted, prompt and meaningful monitoring system is available for the recognition and description of the occurrence of ARI and concomitantly of influenza. An extension of this surveillance to other pathogens or disease scenarios is possible.

Disease Outbreaks↗

PubMed2006

Crossing the species barrier: the threat of an avian influenza pandemic.

Avian influenza (H5N1) has recently been recognized as a new emerging infectious disease that may pose a threat to international public health. Most recent developments lead to the belief that H5N1 could become the cause of the next influenza pandemic. This review discusses the characteristics of H5N1 avian influenza virus as an emerging infectious disease with the potential for pandemic development. In addition, the current pandemic influenza alert status and guidelines for pandemic preparedness, treatment, and prevention are discussed.

Journal Article↗

PubMed2006

Role of the laboratory in diagnosis of influenza during seasonal epidemics and potential pandemics.

Laboratory diagnosis of influenza is critical to its treatment and surveillance. With the emergence of novel and highly pathogenic avian influenza viruses, the role of the laboratory has been further extended to include isolation and subtyping of the virus to monitor its appearance and facilitate appropriate vaccine development. Recent progress in enhancing testing for influenza promises to both improve the management of patients with influenza and decrease associated health care costs. The present review covers the technological characteristics and utilization features of currently available diagnostic tests, the factors that influence the selection of such tests, and the developments that are essential for pandemic preparedness.

Animals↗

PubMed2006

Influenza: current threat from avian influenza.

Influenza is an infectious respiratory pathogen causing annual outbreaks and infrequent pandemics, resulting in significant morbidity, mortality and burdens on the delivery of health care. The geographical spread of highly pathogenic avian influenza (HPAI) H5N1 among poultry and wild bird populations is unprecedented. Growing numbers of sporadic avian influenza infections are occurring in humans, increasing the threat of the next influenza pandemic. Vaccines are the principle means of combating influenza, and a number of studies with H5N1 vaccine candidates are underway. Antiviral agents can be used to treat influenza infection and can be taken as chemoprophylaxis during influenza outbreaks. Oseltamivir has been stockpiled as part of influenza pandemic preparedness planning; however, the emergence of drug resistance may limit its clinical use.

Animals↗

PubMed2026

Programmatic access to ICTV virus taxonomy through a public ontology API.

BACKGROUND: The International Committee on Taxonomy of Viruses (ICTV) is responsible for developing and maintaining a universal virus taxonomy. As the reference framework for organising the viral world, it is essential for virology and related fields. Despite its widespread use in research and public health, programmatic access to ICTV taxonomy has remained limited, posing challenges for integration, versioning, and interoperability across databases and bioinformatics resources requiring up-to-date virus taxonomy. FINDINGS: To address this, we developed a public and sustainable solution leveraging ontology-based APIs. All available ICTV Master Species List (MSL) releases, from MSL1 to MSL41, were transformed into a unified, semantically structured ontology comprising more than 195,000 current and historical entities and deployed through the Ontology Lookup Service (OLS). The ontology is automatically rebuilt and republished whenever a new MSL release becomes available. Complementary ICTV-NCBI mappings and helper libraries support integration into downstream systems. CONCLUSIONS: Together, these resources enable, for the first time, public programmatic retrieval of current and historical ICTV taxon names, taxonomic relationships, metadata, and persistent identifiers through stable endpoints, including resolution of former taxonomic terms to their current accepted taxon or taxa and retrieval of taxon histories across releases. More broadly, this work illustrates a general strategy for transforming structured biological datasets into semantically enriched graph resources exposed through scalable public APIs. These developments enhance interoperability, reduce manual curation, and support FAIR-aligned taxonomic data management in virology and pandemic preparedness.

API↗