scholarly journals Protective Immunity Based on the Conserved Hemagglutinin Stalk Domain and Its Prospects for Universal Influenza Vaccine Development

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Madhu Khanna ◽  
Sachin Sharma ◽  
Binod Kumar ◽  
Roopali Rajput
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Natural Infection ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Influenza B ◽  
Universal Vaccine ◽  
Virus Surface ◽  
Head Domain ◽  
Globular Head

Influenza virus surface glycoprotein hemagglutinin (HA) is an excellent and chief target thatelicitsneutralizing antibodies during vaccination or natural infection. Its HA2 subunit (stem domain) is most conserved as compared to HA1 subunit (globular head domain). Current influenza vaccine relies on globular head domain that provides protection only against the homologous vaccine strains, rarely provides cross-protection against divergent strains, and needs to be updated annually. There is an urge for a truly universal vaccine that provides broad cross-protection against different subtype influenza A viruses along with influenza B viruses and need not be updated annually. Antibodies against the stem domain of hemagglutinin (HA) are able to neutralize a wide spectrum of influenza virus strains and subtypes. These stem-specific antibodies have great potential for the development of universal vaccine against influenza viruses. In this review, we have discussed the stem-specific cross-reactive antibodies and heterosubtypic protection provided by them. We have also discussed their epitope-based DNA vaccine and their future prospects in this scenario.

scholarly journals Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

2015 ◽  
Vol 90 (2) ◽  
pp. 851-861 ◽  
Author(s):  
Teddy John Wohlbold ◽  
Veronika Chromikova ◽  
Gene S. Tan ◽  
Philip Meade ◽  
Fatima Amanat ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monoclonal Antibodies ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Morbidity And Mortality ◽  
Head Domain ◽  
Group 2 ◽  
Reactive Antibody ◽  
Globular Head

ABSTRACTBetween November 2013 and February 2014, China reported three human cases of H10N8 influenza virus infection in the Jiangxi province, two of which were fatal. Using hybridoma technology, we isolated a panel of H10- and N8-directed monoclonal antibodies (MAbs) and further characterized the binding reactivity of these antibodies (via enzyme-linked immunosorbent assay) to a range of purified virus and recombinant protein substrates. The H10-directed MAbs displayed functional hemagglutination inhibition (HI) and neutralization activity, and the N8-directed antibodies displayed functional neuraminidase inhibition (NI) activity against H10N8. Surprisingly, the HI-reactive H10 antibodies, as well as a previously generated, group 2 hemagglutinin (HA) stalk-reactive antibody, demonstrated NI activity against H10N8 and an H10N7 strain; this phenomenon was absent when virus was treated with detergent, suggesting the anti-HA antibodies inhibited neuraminidase enzymatic activity through steric hindrance. We tested the prophylactic efficacy of one representative H10-reactive, N8-reactive, and group 2 HA stalk-reactive antibodyin vivousing a BALB/c challenge model. All three antibodies were protective at a high dose (5 mg/kg). At a low dose (0.5 mg/kg), only the anti-N8 antibody prevented weight loss. Together, these data suggest that antibody targets other than the globular head domain of the HA may be efficacious in preventing influenza virus-induced morbidity and mortality.IMPORTANCEAvian H10N8 and H10N7 viruses have recently crossed the species barrier, causing morbidity and mortality in humans and other mammals. Although these reports are likely isolated incidents, it is possible that more cases may emerge in future winter seasons, similar to H7N9. Furthermore, regular transmission of avian influenza viruses to humans increases the risk of adaptive mutations and reassortment events, which may result in a novel virus with pandemic potential. Currently, no specific therapeutics or vaccines are available against the H10N8 influenza virus subtype. We generated a panel of H10- and N8-reactive MAbs. Although these antibodies may practically be developed into therapeutic agents, characterizing the protective potential of MAbs that have targets other than the HA globular head domain will provide insight into novel antibody-mediated mechanisms of protection and help to better understand correlates of protection for influenza A virus infection.

scholarly journals Computationally Optimized Broadly Reactive Hemagglutinin Elicits Hemagglutination Inhibition Antibodies against a Panel of H3N2 Influenza Virus Cocirculating Variants

2017 ◽  
Vol 91 (24) ◽  
Author(s):  
Terianne M. Wong ◽  
James D. Allen ◽  
Anne-Gaelle Bebin-Blackwell ◽  
Donald M. Carter ◽  
Timothy Alefantis ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Influenza B ◽  
Wild Type ◽  
Protective Antibodies ◽  
H3n2 Influenza ◽  
H3n2 Influenza Virus

ABSTRACT Each influenza season, a set of wild-type viruses, representing one H1N1, one H3N2, and one to two influenza B isolates, are selected for inclusion in the annual seasonal influenza vaccine. In order to develop broadly reactive subtype-specific influenza vaccines, a methodology called computationally optimized broadly reactive antigens (COBRA) was used to design novel hemagglutinin (HA) vaccine immunogens. COBRA technology was effectively used to design HA immunogens that elicited antibodies that neutralized H5N1 and H1N1 isolates. In this report, the development and characterization of 17 prototype H3N2 COBRA HA proteins were screened in mice and ferrets for the elicitation of antibodies with HA inhibition (HAI) activity against human seasonal H3N2 viruses that were isolated over the last 48 years. The most effective COBRA HA vaccine regimens elicited antibodies with broader HAI activity against a panel of H3N2 viruses than wild-type H3 HA vaccines. The top leading COBRA HA candidates were tested against cocirculating variants. These variants were not efficiently detected by antibodies elicited by the wild-type HA from viruses selected as the vaccine candidates. The T-11 COBRA HA vaccine elicited antibodies with HAI and neutralization activity against all cocirculating variants from 2004 to 2007. This is the first report demonstrating broader breadth of vaccine-induced antibodies against cocirculating H3N2 strains compared to the wild-type HA antigens that were represented in commercial influenza vaccines. IMPORTANCE There is a need for an improved influenza vaccine that elicits immune responses that recognize a broader number of influenza virus strains to prevent infection and transmission. Using the COBRA approach, a set of vaccines against influenza viruses in the H3N2 subtype was tested for the ability to elicit antibodies that neutralize virus infection against not only historical vaccine strains of H3N2 but also a set of cocirculating variants that circulated between 2004 and 2007. Three of the H3N2 COBRA vaccines recognized all of the cocirculating strains during this era, but the chosen wild-type vaccine strains were not able to elicit antibodies with HAI activity against these cocirculating strains. Therefore, the COBRA vaccines have the ability to elicit protective antibodies against not only the dominant vaccine strains but also minor circulating strains that can evolve into the dominant vaccine strains in the future.

scholarly journals Generation of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Pui Wang ◽  
Min Zheng ◽  
Siu-Ying Lau ◽  
Pin Chen ◽  
Bobo Wing-Yee Mok ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
T Cell ◽  
Protective Immunity ◽  
Influenza A ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Influenza Vaccines ◽  
Influenza B ◽  
Ns1 Protein

ABSTRACT Nonstructural protein 1 (NS1) of influenza virus is a key virulence element with multifunctional roles in virus replication and a potent antagonist of host immune response. Deletion of NS1 (DelNS1) would create a safer and more extensively immunogenic live attenuated influenza virus (LAIV) vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, which has hampered the application of DelNS1 LAIV vaccines in humans. We have developed two master backbones of deleted-NS1 (DelNS1) viral genomes from influenza A or B viruses which contain novel adaptive mutations to support DelNS1-LAIV replication. These DelNS1-LAIVs are highly attenuated in human cells in vitro and nonpathogenic in mice but replicate well in vaccine-producing cells. Both influenza A and influenza B DelNS1 LAIVs grow better at 33°C than at 37 to 39°C. Vaccination with DelNS1 LAIV performed once is enough to provide potent protection against lethal challenge with homologous virus and strong long-lasting cross protection against heterosubtypic or antigenically distantly related influenza viruses in mice. Mechanistic investigations revealed that DelNS1-LAIVs induce cross protective neutralizing antibody and CD8+ and CD4+ T cell immunities. Importantly, it has been shown that DelNS1-LAIV can be used to enhance specific anti-influenza immunity through expression of additional antigens from the deleted-NS1 site. Generation of DelNS1 viruses which are nonpathogenic and able to grow in vaccine-producing systems is an important strategy for making highly immunogenic LAIV vaccines that induce broad cross protective immunity against seasonal and emerging influenza. IMPORTANCE Current seasonal influenza vaccines are suboptimal and low in immunogenicity and do not provide long-lasting immunity and cross protection against influenza virus strains that have antigenically drifted. More-effective influenza vaccines which can induce both humoral immunity and T cell immunity are needed. The NS1 protein of influenza virus is a virulence element and the critical factor for regulation of the host immune response during virus infection. Deletion of the NS1 protein is a strategy to make an optimal LAIV vaccine. However, DelNS1 viruses are very difficult to grow in regular vaccine-producing systems, hampering the application of DelNS1 LAIV vaccines in humans. We have generated a panel of both influenza A and influenza B DelNS1 LAIVs which are able to grow in regular vaccine-producing cells. These DelNS1 LAIV vaccines are completely nonpathogenic, exhibit potent and long-lasting immunity, and can be used to express extra viral antigen to induce cross protective immunity against seasonal and emerging influenza.

scholarly journals Relationships between Influenza viruses A and B and Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2): sequence homologies and implications for medicine treatment

2020 ◽  
Author(s):  
Makiko TAKECHI ◽  
Shinya NAGASAKI ◽  
Kibo Nagasaki
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Lipid Membrane ◽  
Surface Protein ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Surface ◽  
B Virus ◽  
Coronavirus Infection

In this study, the functions of some segments of coronavirus were cleared by the comparison of homology among genes and proteins of influenza A and influenza B virus and SARS-CoV-2/covid-19(coronavirus). In addition, it is shown of existence of the identity segments across three viruses .It is suggested the possibility of being created that a new DNA vaccine ,a new RNA vaccine and a new medicine against common parts will　be made which are effective against three viruses.Relative high homology among them suggests a possibility that people who were suffered from influenza A or influenza B infection within these from 1 to 2 years would be mildly affected by coronavirus.However, the influenza vaccine is an inactivated vaccine. The influenza vaccine is consisting of NTR (non translated region). It was proved the vaccine is not effective for the treatment of coronavirus infection.On the other hand, in particular, coronavirus segment 9 has a protein close of NP 1.2.3) (nucleocapsid protein) in influenza B virus, and coronavirus segment 11 has a protein close of NA1.2.3) and NB3) which are influenza A or B virus surface protein encoded in the lipid membrane of the virus particles. The result of this study is shown that the possibility of the anti-influenza medicine is effective for medication for the coronavirus infection until the specific medicine for coronavirus infection is approved.

scholarly journals H1 Hemagglutinin Priming Provides Long-Lasting Heterosubtypic Immunity against H5N1 Challenge in the Mouse Model

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e02090-20
Author(s):  
Juan Manuel Carreño ◽  
Shirin Strohmeier ◽  
Ericka Kirkpatrick Roubidoux ◽  
Rong Hai ◽  
Peter Palese ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Natural Infection ◽  
Severe Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Immune Memory ◽  
Influenza B Virus ◽  
Influenza B ◽  
Host Immune System

ABSTRACTInfluenza virus infections leave a signature of immune memory that influences future responses to infections with antigenically related strains. It has been hypothesized that the first exposure in life to H1N1 influenza virus imprints the host immune system, potentially resulting in protection from severe infection with H5N1 later in life through hemagglutinin (HA) stalk-specific antibodies. To study the specific role of the HA on protection against infection without interference of cellular immunity or humoral antineuraminidase immunity, we primed mice with influenza B viruses that express an H1 HA (group 1; B-H1), H3 HA (group 2; B-H3), or wild-type influenza B virus and subsequently challenged them at different time points with an H5N1 virus. Weight loss and survival monitoring showed that the B-H1-primed mice exhibited better protection against H5N1 compared to the control mice. Analysis of H5-specific serum IgG, before and 21 days after H5N1 challenge, evidenced the presence of anti-stalk H5 cross-reactive antibodies in the BH-1 group that were boosted by H5N1 infection. The increased immune responses and protection induced by priming with the B-H1 viruses lasted at least up to 1 year. Hence, a single HA priming based on natural infection induces long-lasting protective immunity against heterosubtypic strains from the same phylogenetic HA group in mice. This study gives mechanistic support to the earlier finding in humans that imprinting by H1 HA protects against H5N1 infections and that highly conserved regions on the HA, like the stalk, are involved in this phenomenon.IMPORTANCE Current studies point out that an HA-mediated immunological imprint is established early in life during the first exposure to influenza viruses, which critically shapes and biases future immune responses. However, studies in animal models are limited and the precise mechanisms of this phenomenon are under investigation. Studies that explore the effect of HA-specific immunity induced during natural infection on future exposures to heterosubtypic influenza strains are needed.

scholarly journals Effectiveness of influenza vaccine in preventing medically-attended influenza virus infection in primary care, Israel, influenza seasons 2014/15 and 2015/16

2018 ◽  
Vol 23 (7) ◽  
Author(s):  
Hamutal Yaron-Yakoby ◽  
Hanna Sefty ◽  
Rakefet Pando ◽  
Rita Dichtiar ◽  
Mark A Katz ◽  
...  
Keyword(s):  
Primary Care ◽  
Influenza Virus ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Season ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Influenza B ◽  
Negative Case ◽  
Influenza A H1n1

Introduction Influenza vaccine is recommended for the entire population in Israel. We assessed influenza vaccine effectiveness (VE) for the 2014/15 and 2015/16 seasons in Israel, for the first time. Methods: Combined nose and throat swab specimens were collected from patients with influenza-like illness (ILI) presenting to sentinel primary care clinics and tested for influenza virus by RT-PCR. VE of the trivalent inactivated vaccine (TIV) was assessed using test-negative case–control design. Results: During the 2014/15 season 1,142 samples were collected; 327 (28.6%) were positive for influenza, 83.8% A(H3N2), 5.8% A(H1N1)pdm09, 9.2% B and 1.2% A un-subtyped. Adjusted VE against all influenza viruses for this influenza season was −4.8% (95% confidence interval (CI): −54.8 to 29.0) and against influenza A(H3N2), it was −15.8% (95% CI: −72.8 to 22.4). For the 2015/16 season, 1,919 samples were collected; 853 (44.4%) were positive for influenza, 43.5% A(H1N1)pdm09, 57% B, 0.7% A(H3N2) and 11 samples positive for both A(H1N1)pdm09 and B. Adjusted VE against all influenza viruses for this influenza season was 8.8% (95% CI: −25.1 to 33.5), against influenza A(H1N1)pdm09, it was 32.3% (95% CI: (−4.3 to 56.1) and against influenza B, it was −2.2% (95% CI: (−47.0 to 29.0). Conclusions: Using samples from patients with ILI visiting sentinel clinics in Israel, we demonstrated the feasibility of influenza VE estimation in Israel.

scholarly journals A Live-Attenuated Prime, Inactivated Boost Vaccination Strategy with Chimeric Hemagglutinin-Based Universal Influenza Virus Vaccines Provides Protection in Ferrets: A Confirmatory Study

Vaccines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 47 ◽  
Author(s):  
Raffael Nachbagauer ◽  
Florian Krammer ◽  
Randy Albrecht
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Virus Vaccine ◽  
Influenza Viruses ◽  
Inactivated Vaccine ◽  
Upper Respiratory Tract ◽  
Live Attenuated Vaccine ◽  
Virus Surface ◽  
Virus Challenge ◽  
Attenuated Vaccine

Influenza viruses cause severe diseases and mortality in humans on an annual basis. The current influenza virus vaccines can confer protection when they are well-matched with the circulating strains. However, due to constant changes of the virus surface glycoproteins, the vaccine efficacy can drop substantially in some seasons. In addition, the current seasonal influenza virus vaccines do not protect from avian influenza viruses of human pandemic potential. Novel influenza virus vaccines that aim to elicit antibodies against conserved epitopes like the hemagglutinin stalk could not only reduce the burden of drifted seasonal viruses but potentially also protect humans from infection with zoonotic and emerging pandemic influenza viruses. In this paper, we generated influenza virus vaccine constructs that express chimeric hemagglutinins consisting of exotic, avian head domains and a consistent stalk domain of a seasonal virus. Using such viruses in a sequential immunization regimen can redirect the immune response towards conserved epitopes. In this study, male ferrets received a live-attenuated vaccine virus based on the A/Ann Arbor/6/60 strain expressing a chimeric H8/1 (cH8/1) hemagglutinin, which was followed by a heterologous booster vaccination with a cH5/1N1 formalin inactivated non-adjuvanted whole virus. This group was compared to a second group that received a cH8/1N1 inactivated vaccine followed by a cH5/1N1 inactivated vaccine. Both groups showed a reduction in viral titers in the upper respiratory tract after the A(H1N1)pdm09 virus challenge. Animals that received the live-attenuated vaccine had low or undetectable titers in the lower respiratory tract. The results support the further development of chimeric hemagglutinin-based vaccination strategies. The outcome of this study confirms and corroborates findings from female ferrets primed with a A/Leningrad/134/17/57-based live attenuated cH8/1N1 vaccine followed by vaccination with an AS03-adjuvanted cH5/1N1 split virus vaccine 10.

scholarly journals Influenza: An Emerging and Re-emerging Public Health Threat in Nepal

2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Winter Season ◽  
Emerging Infectious Diseases ◽  
Influenza Viruses ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Influenza A H1n1 ◽  
New Variant ◽  
Seasonal Epidemics

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.

scholarly journals Haemagglutination-inhibition antibodies against influenza A and influenza B in maternal and neonatal sera

1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten
Keyword(s):  
Influenza Virus ◽  
Maternal Age ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus ◽  
Duration Of Pregnancy ◽  
Pregnancy And Birth

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.

scholarly journals A Host-Restricted Self-Attenuated Influenza Virus Provides Broad Pan-Influenza A Protection in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjin Kim ◽  
Yucheol Cheong ◽  
Jinhee Lee ◽  
Jongkwan Lim ◽  
Sanguine Byun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Infection Model ◽  
Wild Type ◽  
Group 1

Influenza virus infections can cause a broad range of symptoms, form mild respiratory problems to severe and fatal complications. While influenza virus poses a global health threat, the frequent antigenic change often significantly compromises the protective efficacy of seasonal vaccines, further increasing the vulnerability to viral infection. Therefore, it is in great need to employ strategies for the development of universal influenza vaccines (UIVs) which can elicit broad protection against diverse influenza viruses. Using a mouse infection model, we examined the breadth of protection of the caspase-triggered live attenuated influenza vaccine (ctLAIV), which was self-attenuated by the host caspase-dependent cleavage of internal viral proteins. A single vaccination in mice induced a broad reactive antibody response against four different influenza viruses, H1 and rH5 (HA group 1) and H3 and rH7 subtypes (HA group 2). Notably, despite the lack of detectable neutralizing antibodies, the vaccination provided heterosubtypic protection against the lethal challenge with the viruses. Sterile protection was confirmed by the complete absence of viral titers in the lungs and nasal turbinates after the challenge. Antibody-dependent cellular cytotoxicity (ADCC) activities of non-neutralizing antibodies contributed to cross-protection. The cross-protection remained robust even after in vivo depletion of T cells or NK cells, reflecting the strength and breadth of the antibody-dependent effector function. The robust mucosal secretion of sIgA reflects an additional level of cross-protection. Our data show that the host-restricted designer vaccine serves an option for developing a UIV, providing pan-influenza A protection against both group 1 and 2 influenza viruses. The present results of potency and breadth of protection from wild type and reassortant viruses addressed in the mouse model by single immunization merits further confirmation and validation, preferably in clinically relevant ferret models with wild type challenges.

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