Collaborative study on the cross-reactivity of two influenza B viral components in single radial immunodiffusion assay using quadrivalent influenza vaccines in Japan from 2015/16 to 2021-22 influenza season.

A quadrivalent influenza vaccine (QIV) has been available in Japan since the 2015/2016 influenza season. Single radial immunodiffusion (SRID) assays are currently used worldwide to measure the hemagglutinin (HA) content of influenza vaccine components because they are simple, accurate, and the regulatory requirement, ensuring consistency in manufacture for the HA content. However, the cross-reactivity of antisera against the two lineages of the influenza B virus (IFVB) may cause inaccurate quantification of HA content in QIVs using the SRID assay.

Establishment of Reference Reagents for Single-Radial-Immunodiffusion Assay on the 2022/23 Seasonal Influenza Vaccine in Japan and Their Quality Validation.

Potency tests for influenza vaccines are currently performed using a single-radial immunodiffusion (SRID) assay, which requires a reference antigen and anti-hemagglutinin (HA) serum as reference reagents. Reagents must be newly prepared each time a strain used for vaccine production is modified. Therefore, establishing reference reagents of consistent quality is crucial for conducting vaccine potency tests accurately and precisely.

Regulatory aspects of quality and safety for live recombinant viral vaccines against infectious diseases in Japan.

Recombinant viral vaccines expressing antigens of pathogenic microbes (e.g., HIV, Ebola virus, and malaria) have been designed to overcome the insufficient immune responses induced by the conventional vaccines.

Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing.

The immense adaptability of antigen recognition by antibodies is the basis of the acquired immune system. Despite our understanding of the molecular mechanisms underlying the production of the vast repertoire of antibodies by the acquired immune systems, it has not yet been possible to arrive at a global view of a complete antibody repertoire. In particular, B cell repertoires have been regarded as a black box because of their astronomical number of antibody clones.

Efficient protection of mice from influenza A/H1N1pdm09 virus challenge infection via high avidity serum antibodies induced by booster immunizations with inactivated whole virus vaccine.

The immunogenicities of inactivated whole and split virus vaccines derived from influenza A/H1N1pdm09 virus were compared in a mouse model. We demonstrated the unique properties of whole virus vaccine boosters on the serum memory antibody response in mice. Consistent with previous studies, booster immunization with either whole or split virus vaccines of A/H1N1pdm09 virus produced comparable titers of serum antibodies with hemagglutination inhibition and virus-neutralizing activities.

Distorted antibody repertoire developed in the absence of pre-B cell receptor formation.

The pre-B cell receptor (pre-BCR), consisting of the μ heavy chain (μHC) and the surrogate light chain (SLC, Vpre-B and λ5), plays important roles during B cell development. The formation of the pre-BCR, which enables the nascent immunoglobulin HC to associate with the SLC, is considered a prerequisite for B cell development. However, a significant number of peripheral mature (leaky) B cells exist in SLC-deficient mice.

Deciphering antigen-responding antibody repertoires by using next-generation sequencing and confirming them through antibody-gene synthesis.

Vast diversity and high specificity of antigen recognition by antibodies are hallmarks of the acquired immune system. Although the molecular mechanisms that yield the extremely large antibody repertoires are precisely understood, comprehensive description of the global antibody repertoire generated in individual bodies has been hindered by the lack of powerful measures. To obtain holistic understanding of the antibody-repertoire space, we used next-generation sequencing (NGS) to analyze the deep profiles of naive and antigen-responding repertoires of the IgM, IgG1, and IgG2c classes formed in individual mice.

Development of a sensitive novel diagnostic kit for the highly pathogenic avian influenza A (H5N1) virus.

Background: Sporadic emergence of the highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is a serious concern because of the potential for a pandemic. Conventional or quantitative RT-PCR is the standard laboratory test to detect viral influenza infections. However, this technology requires well-equipped laboratories and highly trained personnel.

Broad cross-reactive epitopes of the H5N1 influenza virus identified by murine antibodies against the A/Vietnam/1194/2004 hemagglutinin.

There is an urgent need for a rapid diagnostic system to detect the H5 subtype of the influenza A virus. We previously developed monoclonal antibodies (mAbs) against the H5 hemagglutinin (HA) for use in a rapid diagnostic kit. In this study, we determined the epitopes of the anti-H5 HA murine mAbs OM-b, AY-2C2, and YH-1A1.

WHO recommendations for the viruses used in the 2013-2014 Northern Hemisphere influenza vaccine: Epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013.

In February the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winter in the Northern Hemisphere. These recommendations are based on data collected by National Influenza Centres (NICs) through the WHO Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations of the 2013-2014 Northern Hemisphere influenza vaccine composition.

Influenza A whole virion vaccine induces a rapid reduction of peripheral blood leukocytes via interferon-α-dependent apoptosis.

Infection with single strand RNA (ssRNA) viruses, such as influenza A virus, is known to induce protective acquired immune responses, including the production of neutralizing antibodies. Vaccination also causes a reduction in the number of peripheral blood leukocytes (PBL) shortly after inoculation, a result which may have undesirable adverse effects. The cellular mechanisms for this response have not been elucidated so far.

WHO recommendations for the viruses to be used in the 2012 Southern Hemisphere Influenza Vaccine: epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from February to September 2011.

In February and September each year the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winters in the Northern and Southern Hemispheres respectively. These recommendations are based on data collected by National Influenza Centres (NIC) through the Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations for the 2012 Southern Hemisphere influenza vaccine composition.

Newly established monoclonal antibodies for immunological detection of H5N1 influenza virus.

The H5N1 subtype of the highly pathogenic (HP) avian influenza virus has been recognized for its ability to cause serious pandemics among humans. In the present study, new monoclonal antibodies (mAbs) against viral proteins were established for the immunological detection of H5N1 influenza virus for research and diagnostic purposes. B-cell hybridomas were generated from mice that had been hyperimmunized with purified A/Vietnam/1194/2004 (NIBRG-14) virion that had been inactivated by UV-irradiation or formaldehyde.

Application of deglycosylation to SDS PAGE analysis improves calibration of influenza antigen standards.

Each year the production of seasonal influenza vaccines requires antigen standards to be available for the potency assessment of vaccine batches. These are calibrated and assigned a value for haemagglutinin (HA) content. The calibration of an antigen standard is carried out in a collaborative study amongst a small number of national regulatory laboratories which are designated by WHO as Essential Regulatory Laboratories (ERLs) for the purposes of influenza vaccine standardisation.

Epitope mapping of neutralizing monoclonal antibody in avian influenza A H5N1 virus hemagglutinin.

The global spread of highly pathogenic avian influenza A H5N1 viruses raises concerns about more widespread infection in the human population. Pre-pandemic vaccine for H5N1 clade 1 influenza viruses has been produced from the A/Viet Nam/1194/2004 strain (VN1194), but recent prevalent avian H5N1 viruses have been categorized into the clade 2 strains, which are antigenically distinct from the pre-pandemic vaccine. To understand the antigenicity of H5N1 hemagglutinin (HA), we produced a neutralizing monoclonal antibody (mAb12-1G6) using the pre-pandemic vaccine.

[The latest trend and prospects of development of influenza vaccine].

Vaccine is the most effective measure against influenza. Current vaccine production is based on chicken eggs and has limitation of scalability. In addition, adaptation of influenza viruses to chicken eggs during passages causes antigenic change of viruses and may reduce the efficiency of vaccination.

Differences in the priming effect of various clades/subclades of inactivated H5N1 vaccine for booster injection with heterologous clades of vaccine strains.

The prime-boost response induced by different combinations of four H5N1 vaccines (NIBRG-14 (clade 1), Indo05/2005(H5N1)/PR8-IBCDC-RG2 (clade 2.1), A/Bar-Headed Goose/Qinhai Lake/1A/05 SJ163222 (clade 2.2), and Anhui01/2005(H5N1)-PR8-IBCDC-RG5 (clade 2.

[Trends and perspectives in development of influenza vaccines].

Currently licensed influenza vaccines in Japan are split-virus vaccine for seasonal influenza and alum-adjuvanted whole-virion vaccine for higly pathogenic avian H5N1 influenza, respectively. There are many challenges to improve the efficacy, safety and productivity of influenza vaccine. Prompt supply of vaccine is required for pandemic use and cell culture-based vaccine provides a useful production system because of the flexibility of scale-up production.

Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide.

Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits.

Immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1, NIBRG-14) vaccine administered by intramuscular or subcutaneous injection.

The immunogenicity and safety profile of an inactivated whole-virion influenza A (H5N1, NIBRG-14) vaccine with alum adjuvant that was administered by IM or SC injection in a phase I clinical study involving 120 healthy Japanese men aged 20-40 years is described. The serological response of the IM group was stronger than that of the SC group. Local adverse events were less severe with IM injection than with SC injection, while similar systemic adverse events were seen in both groups.

A prime-boost vaccination of mice with heterologous H5N1 strains.

We evaluated the priming effect of an H5N1 pandemic vaccine in a mouse model to investigate strategies for influenza pandemic vaccination. For priming, an alum-adjuvanted inactivated whole H5N1 vaccine (NIBRG-14, clade 1) was used. As booster vaccines, several formulations of Indo05/05/2005(H5N1)PR8-IBCDC-RG2 vaccines (clades 2-1)were evaluated, including split, whole, alum-adjuvanted split, and alum-adjuvanted whole vaccines.

Human H5N2 avian influenza infection in Japan and the factors associated with high H5N2-neutralizing antibody titer.

Background: H5N2 avian influenza virus infection of humans has not been reported thus far. The first H5N2 avian influenza infection of poultry in Japan occurred in Ibaraki.

Methods: The subjects were workers at 35 chicken farms in Ibaraki Prefecture, where the H5N2 virus or antibody was isolated from chickens.

Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes.

Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine.

Background: Avian H5N1 influenza A virus is an emerging pathogen with the potential to cause substantial human morbidity and mortality. We evaluated the ability of currently licensed seasonal influenza vaccine to confer cross-protection against highly pathogenic H5N1 influenza virus in mice.

Methods: BALB/c mice were inoculated 3 times, either intranasally or subcutaneously, with the trivalent inactivated influenza vaccine licensed in Japan for the 2005-2006 season.

Intranasal immunization with H5N1 vaccine plus Poly I:Poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge.

The avian H5N1 influenza virus has the potential to cause a new pandemic. Since it is difficult to predict which strain of influenza will cause a pandemic, it is advantageous to produce vaccines that confer cross-protective immunity. Mucosal vaccine administration was reported to induce cross-protective immunity by inducing secretion of IgA at the mucosal surface.