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

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.

scholarly journals Unmasking Stem-Specific Neutralizing Epitopes by Abolishing N-Linked Glycosylation Sites of Influenza Virus Hemagglutinin Proteins for Vaccine Design

2016 ◽  
Vol 90 (19) ◽  
pp. 8496-8508 ◽  
Author(s):  
Wen-Chun Liu ◽  
Jia-Tsrong Jan ◽  
Yun-Ju Huang ◽  
Ting-Hsuan Chen ◽  
Suh-Chin Wu
Keyword(s):  
Influenza Virus ◽  
Neutralizing Antibody ◽  
Influenza Vaccines ◽  
Mutant Proteins ◽  
Fusion Inhibition ◽  
Influenza Virus Hemagglutinin ◽  
Glycosylation Sites ◽  
Antibody Titers ◽  
Virus Strains ◽  
Globular Head

ABSTRACTInfluenza virus hemagglutinin (HA) protein consists of two components, i.e., a globular head region and a stem region that are folded within six disulfide bonds, plus several N-linked glycans that produce a homotrimeric complex structure. While N-linked glycosylation sites on the globular head are variable among different strains and different subtypes, N-linked glycosylation sites in the stem region are mostly well conserved among various influenza virus strains. Targeting highly conserved HA stem regions has been proposed as a useful strategy for designing universal influenza vaccines. Since the HA stem region is constituted by an HA1 N-terminal part and a full HA2 part, we expressed a series of recombinant HA mutant proteins with deleted N-linked glycosylation sites in the HA1 stem and HA2 stem regions of H5N1 and pH1N1 viruses. Unmasking N-glycans in the HA2 stem region (H5 N484A and H1 N503A) was found to elicit more potent neutralizing antibody titers against homologous, heterologous, and heterosubtypic viruses. Unmasking the HA2 stem N-glycans of H5HA but not H1HA resulted in more CR6261-like and FI6v3-like antibodies and also correlated with the increase of cell fusion inhibition activity in antisera. Only H5 N484A HA2 stem mutant protein immunization increased the numbers of antibody-secreting cells, germinal center B cells, and memory B cells targeting the stem helix A epitopes in splenocytes. Unmasking the HA2 stem N-glycans of H5HA mutant proteins showed a significantly improvement in the protection against homologous virus challenges but did so to a less degree for the protection against heterosubtypic pH1N1 virus challenges. These results may provide useful information for designing more effective influenza vaccines.IMPORTANCEN-linked glycosylation sites in the stem regions of influenza virus hemagglutinin (HA) proteins are mostly well conserved among various influenza virus strains. Targeting highly conserved HA stem regions has been proposed as a useful strategy for designing universal influenza vaccines. Our studies indicate that unmasking the HA2 stem N-glycans of recombinant HA proteins from H5N1 and pH1N1 viruses induced more potent neutralizing antibody titers against homologous and heterosubtypic viruses. However, only immunization with the H5N1 HA2 stem mutant protein can refocus B antibody responses to the helix A epitope for inducing more CR6261-like/FI6v3-like and fusion inhibition antibodies in antisera, resulting in a significant improvement for the protection against lethal H5N1 virus challenges. These results may provide useful information for designing more effective influenza vaccines.

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 Selecting and Using the Appropriate Influenza Vaccine for Each Individual

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 971
Author(s):  
Toshiki Sekiya ◽  
Marumi Ohno ◽  
Naoki Nomura ◽  
Chimuka Handabile ◽  
Masashi Shingai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
The Elderly ◽  
Influenza Vaccines ◽  
High Morbidity ◽  
Advantages And Disadvantages ◽  
Community Protection ◽  
Global Threat ◽  
Virus Strains

Despite seasonal influenza vaccines having been routinely used for many decades, influenza A virus continues to pose a global threat to humans, causing high morbidity and mortality each year. The effectiveness of the vaccine is largely dependent on how well matched the vaccine strains are with the circulating influenza virus strains. Furthermore, low vaccine efficacy in naïve populations such as young children, or in the elderly, who possess weakened immune systems, indicates that influenza vaccines need to be more personalized to provide broader community protection. Advances in both vaccine technologies and our understanding of influenza virus infection and immunity have led to the design of a variety of alternate vaccine strategies to extend population protection against influenza, some of which are now in use. In this review, we summarize the progress in the field of influenza vaccines, including the advantages and disadvantages of different strategies, and discuss future prospects. We also highlight some of the challenges to be faced in the ongoing effort to control influenza through vaccination.

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 Immunogenicity and safety of subunit influenza vaccines in pregnant women

2018 ◽  
Vol 4 (2) ◽  
pp. 00060-2017 ◽  
Author(s):  
Mikhail P. Kostinov ◽  
Alexander P. Cherdantsev ◽  
Nelli K. Akhmatova ◽  
Daria A. Praulova ◽  
Aristitsa M. Kostinova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pregnant Women ◽  
Influenza Vaccines ◽  
Group Iii ◽  
Group I ◽  
Increased Risk ◽  
Protective Antibodies ◽  
Group Ii ◽  
High Level ◽  
Virus Strains

Pregnancy is a condition of modulated immune suppression, so this group of patients has increased risk of infectious diseases.Trivalent subunit vaccines, unadjusted Agrippal S1 (group I) and immunoadjuvant Grippol Plus (group II), containing 5 μg of actual influenza virus strains, were administered respectively to 37 and 42 women in the second and third trimester of physiological pregnancy.The administration of subunit influenza vaccines was accompanied by the development of local reactions in no more than 10% of patients, compared with 4.9% of the 41 pregnant women in the placebo group (group III). Systemic reactions were of a general somatic nature, did not differ between vaccinated and placebo groups, and were not associated with vaccination. Physiological births in groups I, II and III were 94.6%, 92.9% and 85.4%, respectively, and the birth rates of children without pathologies were 91.9%, 90.5% and 80.5%, respectively, and were comparable between groups. Vaccination stimulated the production of protective antibodies against influenza virus strains in 64.8–94.5% of patients after immunisation with an unadjusted vaccine and in 72.5–90.0% of patients after the administration of an immunoadjuvant vaccine. After 9 months, antibody levels were recorded in 51.3–72.9% in group I and 54.2–74.2% in group II. Immunisation against influenza in pregnant women provided a high level of seroprotection and seroconversion. Nevertheless, the level of seroprotection against the influenza strain A(H3N2, Victoria) was slightly lower in the group immunised with an unadjusted vaccine compared to those vaccinated with the immunoadjuvant vaccine.

scholarly journals Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

mBio ◽  
2010 ◽  
Vol 1 (1) ◽  
Author(s):  
John Steel ◽  
Anice C. Lowen ◽  
Taia T. Wang ◽  
Mark Yondola ◽  
Qinshan Gao ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Neutralizing Antibodies ◽  
Influenza Virus Vaccine ◽  
Influenza Vaccines ◽  
Host Immune System ◽  
Stalk Domain ◽  
Further Development ◽  
Virus Strains ◽  
Globular Head

ABSTRACTAlthough highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.IMPORTANCECurrent influenza vaccines are effective against only a narrow range of influenza virus strains. It is for this reason that new vaccines must be generated and administered each year. We now report progress toward the goal of an influenza virus vaccine which would protect against multiple strains. Our approach is based on presentation to the host immune system of a region of the influenza virus—called a “headless hemagglutinin” (headless HA)—which is similar among a multitude of diverse strains. We show that vaccination of mice with a headless HA confers protection to these animals against a lethal influenza virus challenge, thereby demonstrating the viability of the approach. Through further development and testing, we predict that a single immunization with a headless HA vaccine will offer effective protection through several influenza epidemics.

scholarly journals Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Santosh Dhakal ◽  
Sabra L. Klein
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Virus Vaccine ◽  
Vaccine Efficacy ◽  
Public Health Problem ◽  
Influenza Virus Vaccine ◽  
Host Factors ◽  
Influenza Vaccines ◽  
Vaccine Type ◽  
Induced Immunity

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

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