Inhibition of ciliary activity in organ cultures of ferret trachea in reference to genetic and biological characters of influenza virus strains

1982 ◽  
Vol 28 (7) ◽  
pp. 809-814 ◽  
Author(s):  
P. Diaz-Rodriguez ◽  
A. Boudreault
Keyword(s):  
Influenza Virus ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Ciliary Activity ◽  
Organ Cultures ◽  
Preliminary Screening ◽  
Cold Adapted ◽  
Activity Inhibition ◽  
Biological Characters ◽  
Virus Strains

As reported previously, attenuated stable inhibitor-resistant influenza viruses can be screened by a 50% ciliary activity inhibition test in ferret tracheal organ cultures. This test was further applied to 5 attenuated cold-adapted influenza strains and to 11 strains with known a percentage of RNA–RNA hybridization with the parental A/PR/8/34 (H0N1) virus strain. Again, with one exception, attenuated strains could be clearly differentiated from virulent ones. It was concluded that virulence of influenza strains for man can be detected using this test regardless of the techniques used to prepare attenuated variants. A preliminary screening of attenuated candidates for live influenza vaccines can be achieved with confidence on ferret tracheal organ cultures.

Live influenza vaccine: screening of attenuated virus strains by a 50% ciliary activity inhibition test in organ cultures of ferret trachea

1979 ◽  
Vol 25 (3) ◽  
pp. 279-284 ◽  
Author(s):  
A. Boudreault
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccines ◽  
Ciliary Activity ◽  
Organ Cultures ◽  
Activity Inhibition ◽  
Attenuated Virus ◽  
Time Required ◽  
Virus Strains ◽  
Better Than

This study of three live attenuated inhibitor-resistant influenza vaccines showed that these preparations are usually antigenic and that they caused no significant reactions when characterized by an index of attenuation equal to or slightly better than 1.0 arbitrarily attributed to the 'reference' attenuated A/Hong Kong/68 strain of Beare and Bynoe. This index, measured in vitro on ferret tracheal rings, is expressed as the ratio of the time required for ciliary activity inhibition of 50% of the rings by the tested candidate vaccine strain and the 'reference' attenuated strain. Induction of heterologous antibodies was also observed. Oral administration of underattenuated preparations did not cause the severe reactions which were observed when the same vaccine was administered intranasally.

scholarly journals Development of a Pan-H1 Influenza Vaccine

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Nicole Darricarrère ◽  
Svetlana Pougatcheva ◽  
Xiaochu Duan ◽  
Rebecca S. Rudicell ◽  
Te-Hui Chou ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
The Past ◽  
Individual Strain ◽  
Humoral Responses ◽  
Virus Strains

ABSTRACT The efficacy of current seasonal influenza vaccines varies greatly, depending on the match to circulating viruses. Although most vaccines elicit strain-specific responses, some present cross-reactive epitopes that elicit antibodies against diverse viruses and remain unchanged and effective for several years. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, we evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine. IMPORTANCE Seasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to improve the breadth of protection against divergent H1N1 viruses, HA-ferritin nanoparticles were made and evaluated in mice against a panel of historical and contemporary influenza virus strains. Trivalent combinations of H1 nanoparticles improved the breadth of immunity against divergent H1 influenza viruses.

scholarly journals Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Lisa Walz ◽  
Sarah-Katharina Kays ◽  
Gert Zimmer ◽  
Veronika von Messling
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Vesicular Stomatitis Virus ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Vaccine Antigen ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Virus Strains

ABSTRACTImmune responses induced by currently licensed inactivated influenza vaccines are mainly directed against the hemagglutinin (HA) glycoprotein, the immunodominant antigen of influenza viruses. The resulting antigenic drift of HA requires frequent updating of the vaccine composition and annual revaccination. On the other hand, the levels of antibodies directed against the neuraminidase (NA) glycoprotein, the second major influenza virus antigen, vary greatly. To investigate the potential of the more conserved NA protein for the induction of subtype-specific protection, vesicular stomatitis virus-based replicons expressing a panel of N1 proteins from prototypic seasonal and pandemic H1N1 strains and human H5N1 and H7N9 isolates were generated. Immunization of mice and ferrets with the replicon carrying the matched N1 protein resulted in robust humoral and cellular immune responses and protected against challenge with the homologous influenza virus with an efficacy similar to that of the matched HA protein, illustrating the potential of the NA protein as a vaccine antigen. The extent of protection after immunization with mismatched N1 proteins correlated with the level of cross-reactive neuraminidase-inhibiting antibody titers. Passive serum transfer experiments in mice confirmed that these functional antibodies determine subtype-specific cross-protection. Our findings illustrate the potential of NA-specific immunity for achieving broader protection against antigenic drift variants or newly emerging viruses carrying the same NA but a different HA subtype.IMPORTANCEDespite the availability of vaccines, annual influenza virus epidemics cause 250,000 to 500,000 deaths worldwide. Currently licensed inactivated vaccines, which are standardized for the amount of the hemagglutinin (HA) antigen, primarily induce strain-specific antibodies, whereas the immune response to the neuraminidase (NA) antigen, which is also present on the viral surface, is usually low. Using NA-expressing single-cycle vesicular stomatitis virus replicons, we show that the NA antigen conferred protection of mice and ferrets against not only the matched influenza virus strains but also viruses carrying NA proteins from other strains of the same subtype. The extent of protection correlated with the level of cross-reactive NA-inhibiting antibodies. This highlights the potential of the NA antigen for the development of more broadly protective influenza vaccines. Such vaccines may also provide partial protection against newly emerging strains with the same NA but a different HA subtype.

scholarly journals Vaccination with Vesicular Stomatitis Virus-Vectored Chimeric Hemagglutinins Protects Mice against Divergent Influenza Virus Challenge Strains

2015 ◽  
Vol 90 (5) ◽  
pp. 2544-2550 ◽  
Author(s):  
Alex B. Ryder ◽  
Raffael Nachbagauer ◽  
Linda Buonocore ◽  
Peter Palese ◽  
Florian Krammer ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Vesicular Stomatitis Virus ◽  
Humoral Immunity ◽  
Influenza Viruses ◽  
Full Length ◽  
Influenza Vaccines ◽  
Serum Antibodies ◽  
Virus Challenge ◽  
Vaccination Strategies ◽  
Vesicular Stomatitis

ABSTRACTSeasonal influenza virus infections continue to cause significant disease each year, and there is a constant threat of the emergence of reassortant influenza strains causing a new pandemic. Available influenza vaccines are variably effective each season, are of limited scope at protecting against viruses that have undergone significant antigenic drift, and offer low protection against newly emergent pandemic strains. “Universal” influenza vaccine strategies that focus on the development of humoral immunity directed against the stalk domains of the viral hemagglutinin (HA) show promise for protecting against diverse influenza viruses. Here, we describe such a strategy that utilizes vesicular stomatitis virus (VSV) as a vector for chimeric hemagglutinin (cHA) antigens. This vaccination strategy is effective at generating HA stalk-specific, broadly cross-reactive serum antibodies by both intramuscular and intranasal routes of vaccination. We show that prime-boost vaccination strategies provide protection against both lethal homologous and heterosubtypic influenza challenge and that protection is significantly improved with intranasal vaccine administration. Additionally, we show that vaccination with VSV-cHAs generates greater stalk-specific and cross-reactive serum antibodies than does vaccination with VSV-vectored full-length HAs, confirming that cHA-based vaccination strategies are superior at generating stalk-specific humoral immunity. VSV-vectored influenza vaccines that express chimeric hemagglutinin antigens offer a novel means for protecting against widely diverging influenza viruses.IMPORTANCEUniversal influenza vaccination strategies should be capable of protecting against a wide array of influenza viruses, and we have developed such an approach utilizing a single viral vector system. The potent antibody responses that these vaccines generate are shown to protect mice against lethal influenza challenges with highly divergent viruses. Notably, intranasal vaccination offers significantly better protection than intramuscular vaccination in a lethal virus challenge model. The results described in this study offer insights into the mechanisms by which chimeric hemagglutinin (HA)-based vaccines confer immunity, namely, that the invariant stalk of cHA antigens is superior to full-length HA antigens at inducing cross-reactive humoral immune responses and that VSV-cHA vaccine-induced protection varies by site of inoculation, and contribute to the further development of universal influenza virus vaccines.

Response of Influenza Vaccines Against Heterovariant Influenza Virus Strains in Adults with Chronic Diseases

2007 ◽  
Vol 27 (5) ◽  
pp. 542-547 ◽  
Author(s):  
V. Baldo ◽  
T. Baldovin ◽  
A. Floreani ◽  
E. Fragapane ◽  
R. Trivello ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Chronic Diseases ◽  
Influenza Vaccines ◽  
Virus Strains

scholarly journals A Prevalent Focused Human Antibody Response to the Influenza Virus Hemagglutinin Head Interface

mBio ◽  
2021 ◽  
Author(s):  
Kevin R. McCarthy ◽  
Jiwon Lee ◽  
Akiko Watanabe ◽  
Masayuki Kuraoka ◽  
Lindsey R. Robinson-McCarthy ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Herd Immunity ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Human Antibody ◽  
Human Influenza ◽  
Human Antibodies ◽  
Influenza Virus Hemagglutinin ◽  
Selection For ◽  
Rapid Appearance

The rapid appearance of mutations in circulating human influenza viruses and selection for escape from herd immunity require prediction of likely variants for an annual updating of influenza vaccines. The identification of human antibodies that recognize conserved surfaces on the influenza virus hemagglutinin (HA) has prompted efforts to design immunogens that might selectively elicit such antibodies.

scholarly journals Use of Computational Matrix Adjustment to Evaluate the Effectiveness of Common Influenza Vaccines against the Emergence of Drift Variants

2014 ◽  
Vol 2 (3) ◽  
pp. 224-228
Author(s):  
Jennifer Tram
Keyword(s):  
Influenza Virus ◽  
New Caledonia ◽  
Solomon Islands ◽  
Protein Sequences ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Local Alignment ◽  
Influenza B ◽  
Antigenic Characterization ◽  
Search Tool

Every year the FDA issues a recommendation for the composition of the year’s common influenza vaccine for influenzas A and B.  The FDA can consistently predict the dominance of a particular strand of influenza virus by taking into account previous years’ antigenic characterization percentages. However, the sudden disappearance of dominant antigens and the sudden emergence of drift variants can disrupt this pattern, which questions the effectiveness of that year’s vaccine. Basic Local Alignment Search Tool was used to compare the protein sequences for hemagglutinin and neuraminidase between the strands in the vaccine and the dominant viral strands. This study examined the effectiveness of vaccines from 2000 to 2012, focusing on the transitions between the B/Yamagata and B/Victoria lineages and A/New Caledonia and A/California lineages (H1N1). Between the years 2005 and 2006, dominance of the B/Yamagata lineage, represented by B/Shanghai/361/2002, disappeared almost entirely. For the 2005-2006 flu season, the CDC recommended a B/Shanghai/361/2002 vaccine which expressed a 98% identity to the dominant influenza B hemagglutinin sequence and a 97% identity to the dominant neuraminidase sequence. From 2007 to 2008, the A/New Caledonia virus declined to 34% of cases while the A/Solomon Islands/3/2006 virus increased to 66%. The A/New Caledonia/20/99 vaccine effectively expressed a 97% identity to the hemagglutinin sequence of A/Solomon Islands/3/2006 strand and a 98% identity to the neuraminidase sequence. This study demonstrates that from 2000 to 2012, despite drift variants in influenza viruses, the CDC-recommended vaccine effectively matches the hemagglutinin and neuraminidase protein sequences of the dominant viruses.DOI: http://dx.doi.org/10.3126/ijasbt.v2i3.10952 Int J Appl Sci Biotechnol, Vol. 2(3): 224-228  

scholarly journals Universal influenza virus neuraminidase vaccine elicits protective immune responses against human seasonal and pre-pandemic strains

2021 ◽  
Author(s):  
Amanda L. Skarlupka ◽  
Anne Gaelle Bebin-Blackwell ◽  
Spencer F. Sumner ◽  
Ted M. Ross
Keyword(s):  
North Carolina ◽  
Influenza Virus ◽  
Vaccine Development ◽  
Surface Protein ◽  
Influenza Virus Vaccine ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Vaccine Antigen ◽  
Viet Nam ◽  
H5n1 Influenza

The hemagglutinin (HA) surface protein is the primary immune target for most influenza vaccines. The neuraminidase (NA) surface protein is often a secondary target for vaccine designs. In this study, computationally optimized broadly reactive antigen methodology was used to generate the N1-I NA vaccine antigen that was designed to cross-react with avian, swine, and human influenza viruses of N1 NA subtype. The elicited antibodies bound to NA proteins derived from A/California/07/2009 (H1N1)pdm09, A/Brisbane/59/2007 (H1N1), A/Swine/North Carolina/154074/2015 (H1N1) and A/Viet Nam/1203/2004 (H5N1) influenza viruses, with NA-neutralizing activity against a broad panel of HXN1 influenza strains. Mice vaccinated with the N1-I COBRA NA vaccine were protected from mortality and viral lung titers were lower when challenged with four different viral challenges: A/California/07/2009, A/Brisbane/59/2007, A/Swine/North Carolina/154074/2015 and A/Viet Nam/1203/2004. Vaccinated mice had little to no weight loss against both homologous, but also cross-NA genetic clade challenges. Lung viral titers were lower compared to the mock vaccinated mice, and at times, equivalent to the homologous control. Thus, the N1-I COBRA NA antigen has the potential to be a complimentary component in a multi-antigen universal influenza virus vaccine formulation that also contains HA antigens. Importance The development and distribution of a universal influenza vaccines would alleviate global economic and public health stress from annual influenza virus outbreaks. The influenza virus NA vaccine antigen allows for protection from multiple HA subtypes and virus host origins, but it has not been the focus of vaccine development. The N1-I NA antigen described here protected mice from direct challenge of four distinct influenza viruses and inhibited the enzymatic activity of a N1 influenza virus panel. The use of the NA antigen in combination with the HA widens the breadth of protection against various virus strains. Therefore, this research opens the door to the development of a longer lasting vaccine with increased protective breadth.

scholarly journals Influenza A Virus Vaccination: Immunity, Protection, and Recent Advances Toward A Universal Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 434 ◽  
Author(s):  
Christopher E. Lopez ◽  
Kevin L. Legge
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Virus Infections ◽  
Universal Vaccine

Influenza virus infections represent a serious public health threat and account for significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. Despite being an important countermeasure to combat influenza virus and being highly efficacious when matched to circulating influenza viruses, current preventative strategies of vaccination against influenza virus often provide incomplete protection due the continuous antigenic drift/shift of circulating strains of influenza virus. Prevention and control of influenza virus infection with vaccines is dependent on the host immune response induced by vaccination and the various vaccine platforms induce different components of the local and systemic immune response. This review focuses on the immune basis of current (inactivated influenza vaccines (IIV) and live attenuated influenza vaccines (LAIV)) as well as novel vaccine platforms against influenza virus. Particular emphasis will be placed on how each platform induces cross-protection against heterologous influenza viruses, as well as how this immunity compares to and contrasts from the “gold standard” of immunity generated by natural influenza virus infection.

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