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

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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Changes of the receptor-binding properties of influenza B virus B/Victoria/504/2000 during adaptation in chicken eggs

Virology ◽

10.1016/j.virol.2009.08.014 ◽

2009 ◽

Vol 394 (2) ◽

pp. 218-226 ◽

Cited By ~ 16

Author(s):

Vladimir Y. Lugovtsev ◽

David F. Smith ◽

Jerry P. Weir

Keyword(s):

Receptor Binding ◽

Influenza B Virus ◽

Influenza B ◽

Binding Properties ◽

B Virus ◽

Chicken Eggs

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Experimental Infection Using Mouse-Adapted Influenza B Virus in a Mouse Model

Viruses ◽

10.3390/v12040470 ◽

2020 ◽

Vol 12 (4) ◽

pp. 470 ◽

Cited By ~ 1

Author(s):

Elena Prokopyeva ◽

Olga Kurskaya ◽

Ivan Sobolev ◽

Mariia Solomatina ◽

Tatyana Murashkina ◽

...

Keyword(s):

Influenza Vaccine ◽

Drug Testing ◽

Protective Efficacy ◽

Influenza B Virus ◽

Infection Model ◽

Influenza B ◽

Post Inoculation ◽

B Virus

Every year, influenza B viruses (IBVs) contribute to annual illness, and infection can lead to serious respiratory disease among humans. More attention is needed in several areas, such as increasing virulence or pathogenicity of circulating B viruses and developing vaccines against current influenza. Since preclinical trials of anti-influenza drugs are mainly conducted in mice, we developed an appropriate infection model, using an antigenically-relevant IBV strain, for furtherance of anti-influenza drug testing and influenza vaccine protective efficacy analysis. A Victoria lineage (clade 1A) IBV was serially passaged 17 times in BALB/c mice, and adaptive amino acid substitutions were found in hemagglutinin (HA) (T214I) and neuraminidase (NA) (D432N). By electron microscopy, spherical and elliptical IBV forms were noted. Light microscopy showed that mouse-adapted IBVs caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load, and histopathological features of mouse-adapted IBVs and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of an investigational anti-influenza drug (oseltamivir ethoxysuccinate) and an influenza vaccine (Ultrix®, SPBNIIVS, Saint Petersburg, Russia) showed effectiveness against the mouse-adapted influenza B virus.

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

Journal of Hygiene ◽

10.1017/s0022172400028709 ◽

1970 ◽

Vol 68 (2) ◽

pp. 233-244 ◽

Cited By ~ 17

Author(s):

Jean C. Downie ◽

C. H. Stuart-Harris

Keyword(s):

Neutralizing Antibodies ◽

Nasal Secretion ◽

Influenza B Virus ◽

Influenza B ◽

Serum Antibodies ◽

Live Virus ◽

B Virus ◽

Before And After ◽

Resistance To Infection ◽

High Level

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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The hemagglutinin of influenza B virus present in clinical material is a single species identical to that of mammalian cell-grown virus

Virology ◽

10.1016/0042-6822(90)90270-2 ◽

1990 ◽

Vol 179 (1) ◽

pp. 35-40 ◽

Cited By ~ 48

Author(s):

James S. Robertson ◽

Janet S. Bootman ◽

Carolyn Nicolson ◽

Diane Major ◽

Edwin W. Robertson ◽

...

Keyword(s):

Mammalian Cell ◽

Single Species ◽

Clinical Material ◽

Influenza B Virus ◽

Influenza B ◽

B Virus

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Reassortment compatibility between PB1, PB2, and HA genes of the two influenza B virus lineages in mammalian cells

Scientific Reports ◽

10.1038/srep27480 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 6

Author(s):

Jin Il Kim ◽

Ilseob Lee ◽

Sehee Park ◽

Joon-Yong Bae ◽

Kirim Yoo ◽

...

Keyword(s):

Mammalian Cells ◽

Influenza B Virus ◽

Influenza B ◽

B Virus

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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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Experimental Infection of Adapted Influenza B Virus in Mice Model

10.20944/preprints202002.0022.v1 ◽

2020 ◽

Author(s):

Elena Prokopyeva ◽

Olga Kurskaya ◽

Ivan Sobolev ◽

Mariia Solomatina ◽

Tatyana Murashkina ◽

...

Keyword(s):

Protective Efficacy ◽

Electron Microscopic Examination ◽

Influenza B Virus ◽

Influenza B ◽

Post Inoculation ◽

Mice Model ◽

Electron Microscopic ◽

B Virus

Over the years influenza B virus (IBV) contribute annual disease and can lead to serious respiratory disease among humans. More attention should be paid to the mammalian adaptive processes of B viruses and development of vaccines against current influenza. Because of preclinical trials of anti-influenza drugs are conducted mainly on mice, we developed adequate animal model using antigenically-relevant IBV strain for testing anti-influenza drugs and protective efficacy of flu vaccines. We serially passaged Victoria lineage (clade 1A) IBV 17 times in BALB/c mice. The adaptive amino acid substitutions were found in HA (T214I) and NA (D432N). By the electron microscopic examination, we showed spherical and elliptical shapes of IBV. Light microscopy showed that mouse-adapted B virus caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load and histopathological features of mouse-adapted IBV and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of investigational anti-influenza drug oseltamivir ethoxisuccinate and flu vaccine Ultrix® revealed effectivity against our mouse-adapted influenza B virus.

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