scholarly journals Recombinant Sindbis Viruses Expressing a Cytotoxic T-Lymphocyte Epitope of a Malaria Parasite or of Influenza Virus Elicit Protection against the Corresponding Pathogen in Mice

1998 ◽  
Vol 72 (8) ◽  
pp. 6907-6910 ◽  
Author(s):  
Moriya Tsuji ◽  
Cornelia C. Bergmann ◽  
Yoshiko Takita-Sonoda ◽  
Ken-Ichiro Murata ◽  
Elaine G. Rodrigues ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Cytotoxic T Lymphocyte ◽  
Subcutaneous Administration ◽  
Plasmodium Yoelii ◽  
T Cell Response ◽  
Degree Of Protection ◽  
Histocompatibility Complex ◽  
Protection Against Infection ◽  
High Degree

ABSTRACT Subcutaneous administration in mice of recombinant Sindbis viruses expressing a class I major histocompatibility complex-restricted 9-mer epitope of the Plasmodium yoelii circumsporozoite protein or the nucleoprotein of influenza virus induces a large epitope-specific CD8+ T-cell response. This immunization also elicits a high degree of protection against infection with malaria or influenza A virus.

scholarly journals Influenza virus hemagglutinin-specific cytotoxic T cell response induced by polypeptide produced in Escherichia coli.

1985 ◽  
Vol 162 (2) ◽  
pp. 663-674 ◽  
Author(s):  
A Yamada ◽  
M R Ziese ◽  
J F Young ◽  
Y K Yamada ◽  
F A Ennis
Keyword(s):  
Influenza Virus ◽  
Recombinant Dna ◽  
Cytotoxic T Lymphocyte ◽  
Nonstructural Protein ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Protein Immunization ◽  
Recombinant Dna Techniques

We have tested the abilities of various polypeptides of A/PR/8/34 (H1N1) virus, constructed by recombinant DNA techniques, to induce influenza virus-specific secondary cytotoxic T lymphocyte (CTL) responses. A hybrid protein (c13 protein), consisting of the first 81 amino acids of viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutinin (HA), induced H-2-restricted, influenza virus subtype-specific secondary CTL in vitro, although other peptides did not. Using a recombinant virus, the viral determinant responsible for recognition was mapped to the HA2 portion of c13 protein. Immunization of mice with c13 protein induced the generation of memory CTL in vivo. The CTL precursor frequencies of A/PR/8/34 virus- and c13 protein-immune mice were estimated as one in 8,047 and 50,312, respectively. These results indicate that c13 protein primed recipient mice, even though the level of precursor frequency was below that observed in virus-immune mice.

scholarly journals Murine cytotoxic T lymphocyte recognition of individual influenza virus proteins. High frequency of nonresponder MHC class I alleles.

1988 ◽  
Vol 168 (5) ◽  
pp. 1935-1939 ◽  
Author(s):  
J R Bennink ◽  
J W Yewdell
Keyword(s):  
Influenza Virus ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocyte ◽  
Critical Factor ◽  
Class I ◽  
Foreign Protein ◽  
Outbred Populations ◽  
High Degree ◽  
Ctl Responses ◽  
Virus Proteins

We determined the MHC restriction of CTL responses to five individual influenza virus proteins. Four viral proteins failed to be recognized in conjunction with three of the five class I alleles of the H-2k and H-2d haplotypes, while the fifth was recognized only in conjunction with a single allele. This indicates that there is a significant chance that a given class I allele will be associated with low responsiveness or nonresponsiveness for a given foreign protein. This explains, at least in part, why MHC-linked nonresponsiveness is frequently detected in polyclonal antiviral CTL responses. Most importantly, these findings support the idea that responsiveness to foreign antigens is a critical factor in maintaining the high degree of MHC class I polymorphism in outbred populations.

scholarly journals Hyperattenuated Recombinant Influenza A Virus Nonstructural-Protein-Encoding Vectors Induce Human Immunodeficiency Virus Type 1 Nef-Specific Systemic and Mucosal Immune Responses in Mice

2001 ◽  
Vol 75 (19) ◽  
pp. 8899-8908 ◽  
Author(s):  
Boris Ferko ◽  
Jana Stasakova ◽  
Sabine Sereinig ◽  
Julia Romanova ◽  
Dietmar Katinger ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Influenza Virus ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Nonstructural Protein ◽  
T Cell Response ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have generated recombinant influenza A viruses belonging to the H1N1 and H3N2 virus subtypes containing an insertion of the 137 C-terminal amino acid residues of the human immunodeficiency virus type 1 (HIV-1) Nef protein into the influenza A virus nonstructural-protein (NS1) reading frame. These viral vectors were found to be genetically stable and capable of growing efficiently in embryonated chicken eggs and tissue culture cells but did not replicate in the murine respiratory tract. Despite the hyperattenuated phenotype of influenza/NS-Nef viruses, a Nef and influenza virus (nucleoprotein)-specific CD8+-T-cell response was detected in spleens and the lymph nodes draining the respiratory tract after a single intranasal immunization of mice. Compared to the primary response, a marked enhancement of the CD8+-T-cell response was detected in the systemic and mucosal compartments, including mouse urogenital tracts, if mice were primed with the H1N1 subtype vector and subsequently boosted with the H3N2 subtype vector. In addition, Nef-specific serum IgG was detected in mice which were immunized twice with the recombinant H1N1 and then boosted with the recombinant H3N2 subtype virus. These findings may contribute to the development of alternative immunization strategies utilizing hyperattenuated live recombinant influenza virus vectors to prevent or control infectious diseases, e.g., HIV-1 infection.

scholarly journals Simultaneous expression of H-2-restricted and alloreactive recognition by a cloned line of influenza virus-specific cytotoxic T lymphocytes.

1981 ◽  
Vol 153 (5) ◽  
pp. 1371-1376 ◽  
Author(s):  
T J Braciale ◽  
M E Andrew ◽  
V L Braciale
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Influenza A ◽  
Direct Evidence ◽  
Cross Reactivity ◽  
Cytotoxic T Cell ◽  
Cell Level ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Theoretical Considerations

Based on theoretical considerations and several types of experimental evidence with heterogeneous cell populations it has been proposed that alloreactive T cells and major histocompatibility complex (MHC)-restricted T cells directed to foreign non-NHC antigens represent overlapping subsets. In this report we provide direct evidence for this hypothesis at the clonal level. We have isolated a cloned continuous influenza virus-specific cytotoxic T cell (CTL) line derived from a single (H-2b X H-2d)F1 CTL precursor which simultaneously exhibits H-2-restricted cytotoxicity of influenza A/Japan/305/57 virus in association with H-2Kd and alloreactive cytotoxicity for H-2Kk alloantigen. Cold target inhibition data demonstrate that both MHC-restricted and alloreactive recognition is mediated by the same cell population. In addition to cross-reactivity at the target cell level, we shown that this cloned CTL line can be specifically stimulated to proliferate either by A/Japan/305/57 virus-infected cells expressing H-2Kd or by uninfected cells of the H-2Kk haplotype.

scholarly journals Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung

2016 ◽  
Vol 90 (20) ◽  
pp. 9364-9382 ◽  
Author(s):  
Stephanie C. Talker ◽  
Maria Stadler ◽  
Hanna C. Koinig ◽  
Kerstin H. Mair ◽  
Irene M. Rodríguez-Gómez ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Virus Infection ◽  
Influenza A ◽  
Vaccine Development ◽  
Influenza Virus Infection ◽  
T Cell Response ◽  
Large Animal ◽  
Ifn Γ

ABSTRACTPigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i.Ex vivoflow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67+) CD8+T cells with an early effector phenotype (perforin+CD27+) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4+and CD8+T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4+and CD8+T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4+and CD8+memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles andin vitroreactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs.IMPORTANCEPigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we provide the first detailed characterization of magnitude, kinetics, and phenotype of specific T cells recruited to the lungs of influenza virus-infected pigs, and we could demonstrate multifunctionality, cross-reactivity, and memory formation of these cells. This, and ensuing work in the pig, will strengthen the position of this species as a large-animal model for human influenza virus infection and will immediately benefit vaccine development for improved control of influenza virus infections in pigs.

scholarly journals Vaccine and Monoclonal Antibody That Enhance Mouse Resistance to Candidiasis

2011 ◽  
Vol 18 (10) ◽  
pp. 1656-1667 ◽  
Author(s):  
Hong Xin ◽  
Jim E. Cutler
Keyword(s):  
Monoclonal Antibody ◽  
Immune Serum ◽  
Terminal Portion ◽  
Partial Protection ◽  
Content Type ◽  
Degree Of Protection ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
High Degree

ABSTRACTPreviously we showed that antibodies specific for the glycan β-1,2-mannotriose [β-(Man)3] on the cell surface ofCandida albicansprotect mice against disseminated candidiasis (H. Xin, S. Dziadek, D. R. Bundle, and J. E. Cutler, Proc. Natl. Acad. Sci. U. S. A. 105:13526–13531, 2008). Furthermore, six 14-mer peptides that are within the N-terminal portion ofC. albicanswall proteins were conjugated to the glycan in an attempt to create immunogenic glycopeptide conjugates. By a dendritic cell (DC)-based immunization approach, all were immunogenic and three of the six conjugates induced a high degree of protection in mice. Interestingly, whereas all six peptides induced antibody responses when used alone to pulse DCs for subsequent immunizations, three peptides induced protection, and one in particular, peptide Fba (derived fromfructose-bisphosphatealdolase), induced robust protective responses and is the focus of the current work. Fba peptide is not restricted by the major histocompatibility complex class II (MHC-II), as it induced anti-Fba antibodies in mice of different H-2 haplotypes and in rabbits. Furthermore, the peptide induced protection against disease caused by differentC. albicansstrains. Partial protection was achieved when alum was used in place of DCs for Fba immunizations. The passive transfer of immune sera from Fba-vaccinated mice, but not immune serum preabsorbed with fungal cells, conferred protection in naïve mice. This result, along with our finding that a monoclonal antibody specific for the peptide, E2-9 (IgM), protected mice against candidiasis, provide strong evidence that antibodies contribute to protection. Our work demonstrates the utility of cell wall peptides alone or as glycopeptides in vaccines designed for the induction of immunity against candidiasis and monoclonal antibodies as a rapid immunoprotective approach against the disease.

scholarly journals Efficient Control of Zika Virus Infection Induced by a Non-Replicating Adenovector Encoding Zika Virus NS1/NS2 Antigens Fused to the MHC Class II-Associated Invariant Chain

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2215
Author(s):  
Loulieta Nazerai ◽  
Søren Buus ◽  
Anette Stryhn ◽  
Allan Randrup Thomsen ◽  
Jan Pravsgaard Christensen
Keyword(s):  
Mhc Class Ii ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
T Cell Response ◽  
Invariant Chain ◽  
Degree Of Protection ◽  
Mhc Ii ◽  
Efficient Control ◽  
High Degree ◽  
Ongoing Concern

It is generally believed that a successful Zika virus (ZIKV) vaccine should induce neutralizing antibodies against the ZIKV envelope (E) protein to efficiently halt viral infection. However, E-specific neutralizing antibodies have been implicated in a phenomenon called antibody-dependent enhancement, which represents an ongoing concern in the flavivirus-vaccinology field. In this report, we investigated the vaccination potential of replication-deficient adenoviral vectors encoding the ZIKV non-structural proteins 1 and 2 (NS1/NS2) and employed the strategy of linking the antigens to the MHC-II associated invariant chain (li) to improve immunogenicity and by inference, the level of protection. We demonstrated that li-linkage enhanced the production of anti-NS1 antibodies and induced an accelerated and prolonged polyfunctional CD8 T cell response in mice, which ultimately resulted in a high degree of protection against ZIKV infection of the CNS.

scholarly journals Sequence Variation in a Newly Identified HLA-B35-Restricted Epitope in the Influenza A Virus Nucleoprotein Associated with Escape from Cytotoxic T Lymphocytes

2002 ◽  
Vol 76 (5) ◽  
pp. 2567-2572 ◽  
Author(s):  
A. C. M. Boon ◽  
G. de Mutsert ◽  
Y. M. F. Graus ◽  
R. A. M. Fouchier ◽  
K. Sintnicolaas ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Influenza A ◽  
Sequence Variation ◽  
Cytotoxic T Lymphocyte ◽  
Chronological Order ◽  
Ctl Epitope ◽  
High Degree ◽  
Restricted Epitope

ABSTRACT Here, we describe a new HLA-B*3501-restricted cytotoxic T lymphocyte (CTL) epitope in the influenza A virus (H3N2) nucleoprotein, which was found to exhibit a high degree of variation at nonanchor residues. The influenza virus variants emerged in chronological order, and CTLs directed against old variants failed to recognize more recent strains of influenza A virus, indicating an escape from CTL immunity.

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