The production of neutralizing activity in serum and nasal secretion following immunization with influenza B virus

SUMMARYTrials were made in volunteers in 1967 and 1968 of various virus vaccines against influenza virus B. Sera and serially collected nasal washings before and after immunization were tested respectively for haemagglutination-inhibiting and tissue culture virus-neutralizing antibodies to the same strain of influenza B/Eng/65 virus as that used in the vaccines. Infection, as determined by recovery of virus and serological changes following intranasal instillation of attenuated live virus, was accompanied by the subsequent appearance of neutralizing antibodies in nasal secretion. Inactivated vaccine subcutaneously did not evoke nasal antibody formation in 1967 but did so in 1968.In 1968 intranasal challenge of the volunteers with the attenuated virus 1 month after immunization demonstrated a correlation of susceptibility or resistance to infection with nasal and serum antibodies. Resistance appeared to depend either on a high level of serum antibodies or nasal antibodies, or both.

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Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach

Journal of Virology ◽

10.1128/jvi.01213-08 ◽

2008 ◽

Vol 82 (21) ◽

pp. 10580-10590 ◽

Cited By ~ 73

Author(s):

Rong Hai ◽

Luis Martínez-Sobrido ◽

Kathryn A. Fraser ◽

Juan Ayllon ◽

Adolfo García-Sastre ◽

...

Keyword(s):

Reverse Genetics ◽

Influenza Viruses ◽

Influenza B Virus ◽

Influenza B ◽

Type I ◽

Live Attenuated Vaccine ◽

Live Virus ◽

B Virus

ABSTRACT Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against infections with these viruses. Here, we report the construction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates. Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. The resulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and in vivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR−/− mice was confirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.

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Immunogenicity and Protective Efficacy in Mice of Influenza B Virus Vaccines Grown in Mammalian Cells or Embryonated Chicken Eggs

Journal of Virology ◽

10.1128/jvi.72.5.4472-4477.1998 ◽

1998 ◽

Vol 72 (5) ◽

pp. 4472-4477 ◽

Cited By ~ 32

Author(s):

I. V. Alymova ◽

S. Kodihalli ◽

E. A. Govorkova ◽

B. Fanget ◽

C. Gerdil ◽

...

Keyword(s):

Mammalian Cell ◽

Mammalian Cells ◽

Neutralizing Antibodies ◽

Protective Efficacy ◽

Influenza B Virus ◽

Influenza B ◽

Homologous Antigen ◽

B Virus ◽

Chicken Eggs ◽

Embryonated Chicken

ABSTRACT The immunogenicity and protective efficacy of formalin-inactivated influenza B/Memphis/1/93 virus vaccines propagated exclusively in Vero cells, MDCK cells, or embryonated chicken eggs (hereafter referred to as eggs) were investigated. Mammalian cell-grown viruses differ from the egg-grown variant at amino acid position 198 (Pro/Thr) in the hemagglutinin gene. The level of neuraminidase activity was highest in egg-grown virus, while MDCK and Vero cell-derived viruses possessed 70 and 90% less activity, respectively. After boosting, each of the vaccines induced high levels of hemagglutinin-inhibiting, neuraminidase-inhibiting, and neutralizing antibodies that provided complete protection from MDCK-grown virus challenge. Mammalian cell-derived virus vaccines induced serum antibodies that were more cross-reactive, while those induced by egg-grown virus vaccines were more specific to the homologous antigen. Enzyme-linked immunospot analysis indicated that cell-grown virus vaccines induced high frequencies of immunoglobulin G (IgG)-producing cells directed against both cell- and egg-grown virus antigens, whereas egg-grown virus vaccine induced higher frequencies of IgG- and IgM-producing cells reacting with homologous antigen and low levels of IgG-producing cells reactive with cell-grown viruses. These studies indicate that influenza B virus variants selected in different host systems can elicit different immune responses, but these alterations had no detectable influence on the protective efficacy of the vaccines with the immunization protocol used in this study.

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Replication-Competent Influenza B Reporter Viruses as Tools for Screening Antivirals and Antibodies

Journal of Virology ◽

10.1128/jvi.02164-15 ◽

2015 ◽

Vol 89 (23) ◽

pp. 12226-12231 ◽

Cited By ~ 11

Author(s):

Benjamin O. Fulton ◽

Peter Palese ◽

Nicholas S. Heaton

Keyword(s):

Economic Burden ◽

Neutralizing Antibodies ◽

Rapid Screening ◽

Influenza B Virus ◽

Influenza B ◽

Human Pathogen ◽

Reporter Virus ◽

Antiviral Compounds ◽

B Virus ◽

Significant Health

Influenza B virus is a human pathogen responsible for significant health and economic burden. Research into this pathogen has been limited by the lack of reporter viruses. Here we describe the development of both a replication-competent fluorescent influenza B reporter virus and bioluminescent influenza B reporter virus. Furthermore, we demonstrate these reporter viruses can be used to quickly monitor viral growth and permit the rapid screening of antiviral compounds and neutralizing antibodies.

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The sequential appearance of antibody and immunoglobins in nasal secretion after immunization of volunteers with live and inactivated influenza B virus vaccines

Journal of Hygiene ◽

10.1017/s0022172400046416 ◽

1973 ◽

Vol 71 (3) ◽

pp. 433-445 ◽

Cited By ~ 5

Author(s):

Jean C. Downie

Keyword(s):

Protein Concentration ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Nasal Secretion ◽

Influenza B Virus ◽

Influenza B ◽

Nasal Wash ◽

Live Attenuated Vaccine ◽

Live Virus ◽

Absorption Studies

SUMMARYThe sequential development of the immune response in nasal washings was studied in 54 volunteers immunized with either attenuated or inactivated influenza B/Eng/13/65 virus vaccines.Eleven of the 15 volunteers given the inactivated vaccine by deep subcutaneous inoculation showed no rise in nasal wash protein or immunoglobins due to the immunization procedure nor was specific neutralizing antibody detected in their nasal washings after immunization. Neutralizing antibody was detected in nasal washings of three volunteers in this group who also showed a 20-fold or greater increase in serum haemagglutinin-inhibiting antibody after immunization and in one volunteer who had antibody present in pre-trial nasal washings.Eleven of 15 volunteers who were successfully infected by the live attenuated vaccine showed a characteristic rise in protein and IgA and IgG immunoglobin concentrations in nasal washings 5–14 days after the administration of the live virus vaccine. Neutralizing antibody was detected in the nasal washings of these 11 volunteers and appeared at the same time as or 1–2 days after the initial rise of protein and immunoglobin. Neutralizing antibody was also detected in the nasal washings of one other volunteer who did not show a rise in protein or immunoglobin concentration in nasal washings after immunization.IgA was detected (⋟ 3 mg./lOO ml.) in the majority (84%) of nasal wash specimens which had a protein concentration of 0·2 mg./ml. or greater while IgG was not detected (⋟ 4·5 mg./lOO ml.) until the protein concentration rose to 0·4 mg./ml. or greater. The geometric mean concentration for normal nasal wash protein in this study was 0·3 + 0·1 mg./ml.Regression analysis indicated that the concentrations of both IgA and IgG immunoglobins were directly proportional to the protein concentration in nasal washings but that this relationship varied considerably between individuals.Absorption studies indicated that neutralizing and haemagglutinin-inhibiting antibodies in nasal secretion to influenza B/Eng/13/65 virus were predominantly associated with the IgA class of immunoglobin.

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Antibody Responses toward the Major Antigenic Sites of Influenza B Virus Hemagglutinin in Mice, Ferrets, and Humans

Journal of Virology ◽

10.1128/jvi.01673-18 ◽

2018 ◽

Vol 93 (2) ◽

Cited By ~ 12

Author(s):

Weina Sun ◽

Davina S. Kang ◽

Allen Zheng ◽

Sean T. H. Liu ◽

Felix Broecker ◽

...

Keyword(s):

Specific Antibody ◽

Hemagglutination Inhibition ◽

Neutralizing Antibodies ◽

Age Groups ◽

Antibody Responses ◽

Antigenic Drift ◽

Influenza B Virus ◽

Influenza B ◽

Antigenic Sites ◽

B Virus

ABSTRACTThe influenza B virus hemagglutinin contains four major antigenic sites (the 120 loop, the 150 loop, the 160 loop, and the 190 helix) within the head domain. These immunodominant antigenic sites are the main targets of neutralizing antibodies and are subject to antigenic drift. Yet little is known about the specific antibody responses toward each site in terms of antibody prevalence and hemagglutination inhibition activity. In this study, we used modified hemagglutinins of influenza B virus which display only one or none of the major antigenic sites to measure antibody responses toward the classical as well as the noncanonical epitopes in mice, ferrets, and humans. With our novel reagents, we found that both hemagglutination inhibition antibodies and total IgGs were mostly induced by the major antigenic sites. However, in human adults, we observed high hemagglutination inhibition antibody responses toward the noncanonical epitopes. By stratifying the human samples into age groups, we found that the noncanonical antibody responses appeared to increase with age.IMPORTANCEThis study dissected the specific antibody responses toward the major antigenic sites and the noncanonical epitopes of influenza B virus hemagglutinin in animals and humans using novel reagents. These findings will guide the design of the next generation of influenza virus vaccines.

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Recurring Influenza B Virus Infections in Seals

Emerging Infectious Diseases ◽

10.3201/eid1903.120965 ◽

2013 ◽

Vol 19 (3) ◽

pp. 511-512 ◽

Cited By ~ 53

Author(s):

Rogier Bodewes ◽

Danny Morick ◽

Gerrie de Mutsert ◽

Nynke Osinga ◽

Theo Bestebroer ◽

...

Keyword(s):

Influenza B Virus ◽

Influenza B ◽

Virus Infections ◽

B Virus

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Molecular Epidemiology and Phylogenetic Analyses of Influenza B Virus in Thailand during 2010 to 2014

PLoS ONE ◽

10.1371/journal.pone.0116302 ◽

2015 ◽

Vol 10 (1) ◽

pp. e0116302 ◽

Cited By ~ 31

Author(s):

Nipaporn Tewawong ◽

Kamol Suwannakarn ◽

Slinporn Prachayangprecha ◽

Sumeth Korkong ◽

Preeyaporn Vichiwattana ◽

...

Keyword(s):

Molecular Epidemiology ◽

Phylogenetic Analyses ◽

Influenza B Virus ◽

Influenza B ◽

B Virus

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Mutation E48K in PB1 Polymerase Subunit Improves Stability of a Candidate Live Attenuated Influenza B Virus Vaccine

Vaccines ◽

10.3390/vaccines9070800 ◽

2021 ◽

Vol 9 (7) ◽

pp. 800

Author(s):

Jongsuk Mo ◽

Stivalis Cardenas-Garcia ◽

Jefferson J. S. Santos ◽

Lucas M. Ferreri ◽

C. Joaquín Cáceres ◽

...

Keyword(s):

Vaccine Candidate ◽

The Elderly ◽

Potential Interaction ◽

Respiratory Pathogen ◽

Influenza B Virus ◽

Influenza B ◽

Epitope Tag ◽

Live Attenuated Vaccine ◽

B Virus ◽

Homologous Challenge

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children, and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of an HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation to stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations, along with attenuating mutations E580G and S660A, in PB1 of B/Bris (B/Bris PB1att 4M). Serial passages of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

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