scholarly journals DNA vaccine encoding Hantavirus glycoprotein N-terminal, targeted to the major histocompatibility complex II compartment by lysosome-associated membrane protein, significantly elicits both specific humoral and cellular immune responses and induces immune protection against Hantavirus challenge in Balb/c mice

2013 ◽  
Vol 4 ◽  
Author(s):  
Jiang Dongbo ◽  
Sun Yuanjie ◽  
Cheng Linfeng ◽  
Yang Kun ◽  
Zhang Fanglin
2002 ◽  
Vol 76 (12) ◽  
pp. 6093-6103 ◽  
Author(s):  
Eishiro Mizukoshi ◽  
Michelina Nascimbeni ◽  
Joshua B. Blaustein ◽  
Kathleen Mihalik ◽  
Charles M. Rice ◽  
...  

ABSTRACT The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major histocompatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-γ) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-γ-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes.


2017 ◽  
Vol 92 (1) ◽  
Author(s):  
Francis Mwimanzi ◽  
Mako Toyoda ◽  
Macdonald Mahiti ◽  
Jaclyn K. Mann ◽  
Jeffrey N. Martin ◽  
...  

ABSTRACTPatient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently than HLA-B. However, it remains unknown whether this property is common to Nef proteins across primate lentiviruses and how antiviral immune responses may be affected. We examined 263 Nef clones from diverse primate lentiviruses including different pandemic HIV-1 group M subtypes for their ability to downregulate major histocompatibility complex class A (MHC-A) and MHC-B from the cell surface. Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC-B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A, on average, 11 to 32% more efficiently than MHC-B. Nef genotype/phenotype analyses in a cohort of HIV-1 subtype C-infected patients (n= 168), together with site-directed mutagenesis, revealed Nef position 9 as a subtype-specific determinant of differential HLA-A versus HLA-B downregulation activity. Nef clones harboring nonconsensus variants at codon 9 downregulated HLA-B (though not HLA-A) significantly better than those harboring the consensus sequence at this site, resulting in reduced recognition of infected target cells by HIV-1-specific CD8+effector cellsin vitro. Among persons expressing protective HLA class I alleles, carriage of Nef codon 9 variants was also associated with reducedex vivoHIV-specific T cell responses. Our results demonstrate that Nef's inferior ability to downregulate MHC-B compared to that of MHC-A is conserved across primate lentiviruses and suggest that this property influences antiviral cellular immune responses.IMPORTANCEPrimate lentiviruses encode the Nef protein that plays an essential role in establishing persistent infection in their respective host species. Nef interacts with the cytoplasmic region of MHC-A and MHC-B molecules and downregulates them from the infected cell surface to escape recognition by host cellular immunity. Using a panel of Nef alleles isolated from diverse primate lentiviruses including pandemic HIV-1 group M subtypes, we demonstrate that Nef proteins across all lentiviral lineages downregulate MHC-A approximately 20% more effectively than MHC-B. We further identify a naturally polymorphic site at Nef position 9 that contributes to the MHC-B downregulation function in HIV-1 subtype C and show that carriage of Nef variants with enhanced MHC-B downregulation ability is associated with reduced breadth and magnitude of MHC-B-restricted cellular immune responses in HIV-infected individuals. Our study underscores an evolutionarily conserved interaction between lentiviruses and primate immune systems that may contribute to pathogenesis.


2006 ◽  
Vol 81 (1) ◽  
pp. 349-361 ◽  
Author(s):  
Roger W. Wiseman ◽  
Jason A. Wojcechowskyj ◽  
Justin M. Greene ◽  
Alex J. Blasky ◽  
Tobias Gopon ◽  
...  

ABSTRACT Nonhuman primates are widely used to study correlates of protective immunity in AIDS research. Successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (MHC) genes results in quantitative and qualitative differences in immune responses. Here we use microsatellite analysis to show that simian immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC genetics, with six common haplotypes accounting for two-thirds of the MHC haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques carry at least one complete copy of the most frequent MHC haplotype, and 8% of these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely conserved in unrelated Indian rhesus macaques. After intrarectal infection with highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus macaques mounted concordant cellular immune responses comparable to those previously reported for a pair of monozygotic twins infected with the same strain of human immunodeficiency virus. Our identification of relatively abundant SIV-susceptible, MHC-identical macaques will facilitate research into protective cellular immunity.


Vaccine ◽  
2016 ◽  
Vol 34 (32) ◽  
pp. 3634-3640 ◽  
Author(s):  
Marie Borggren ◽  
Jens Nielsen ◽  
Ingrid Karlsson ◽  
Tina S. Dalgaard ◽  
Ramona Trebbien ◽  
...  

Vaccine ◽  
2008 ◽  
Vol 26 (49) ◽  
pp. 6225-6231 ◽  
Author(s):  
Krystle A. Lang ◽  
Jian Yan ◽  
Ruxandra Draghia-Akli ◽  
Amir Khan ◽  
David B. Weiner

Vaccine ◽  
2005 ◽  
Vol 23 (14) ◽  
pp. 1649-1656 ◽  
Author(s):  
He Xiao-wen ◽  
Sun Shu-han ◽  
Hu Zhen-lin ◽  
Li Jun ◽  
Jiang Lei ◽  
...  

2000 ◽  
Vol 68 (6) ◽  
pp. 3074-3078 ◽  
Author(s):  
Zhang Dong-Ji ◽  
Xi Yang ◽  
Caixia Shen ◽  
Hong Lu ◽  
Andrew Murdin ◽  
...  

ABSTRACT We previously reported that DNA vaccination was able to elicit cellular immune responses and partial protection againstChlamydia trachomatis infection. However, DNA immunization alone did not generate immune responses or protection as great as that induced by using live organisms. In this study, we evaluated the immunologic effects of a combinational vaccination approach usingC. trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) DNA priming followed by boosting with immune-stimulating complexes (ISCOM) of MOMP protein (MOMP ISCOM) for protection of BALB/c mice against MoPn lung infection. Substantially better protection to challenge infection was observed in mice given combinational vaccination compared with mice given MOMP ISCOM immunization alone, and the protection approximated that induced by live organisms. Enhanced protection was correlated with stronger delayed-type hypersensitivity, higher levels of gamma interferon production, and increased immunoglobulin A antibody responses in lung homogenates. The results indicate that DNA priming followed by ISCOM protein boosting may be useful in designing a fully protective chlamydial vaccine.


2017 ◽  
Vol 27 (3) ◽  
pp. 168-174 ◽  
Author(s):  
Yu Yang ◽  
Zhiqiang Shao ◽  
Jiangping Gao

To improve the lower immune intensity of DNA vaccines, we developed a DNA vaccine based on prostate cancer-specific antigen (PSA), which has been suggested as a potential target for prostate cancer therapy, and enhanced the DNA vaccine potency using interleukin-12 (IL-12) as an intramolecular adjuvant. A series of DNA plasmids encoding human PSA, IL-12, and their conjugates was constructed and injected into female mice intramuscularly, followed by an electric pulse. The humoral and cellular immune responses after immunization were detected by ELISA and ELISPOT, respectively. To evaluate the therapeutic efficacy of these plasmids, a mouse model with a PSA-expressing tumor was constructed. Mice vaccinated with PSA-IL-12 plasmids elicited the strongest PSA-specific humoral and cellular immune responses. Furthermore, these vaccinations inhibited the growth of PSA-expressing tumors and prolonged mouse survival. These observations emphasize the potential of the IL-12 gene as an intramolecular adjuvant for DNA vaccines. Moreover, the vaccine based on PSA and IL-12 may be a promising treatment for prostate cancer.


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