• DNA vaccines
• clinical trials
• hepatitis
• inactivated vaccines
• infection prevention
• mRNA vaccines
• public health
• recombinant vaccines
• vaccinology
• virus‐like particles

• Humans
• Viral Hepatitis Vaccines/immunology
• Hepatitis C/prevention & control
• Hepatitis C/immunology
• Hepacivirus/immunology
• Hepacivirus/genetics
• Vaccine Development
• Antibodies, Neutralizing/immunology
• Vaccines, Subunit/immunology
• Animals
• Vaccines, Inactivated/immunology

• COVID-19
• MVA-based vaccine
• S protein
• SARS-CoV-2
• efficacy
• immunogenicity
• mice
• variants of concern

• Animals
• Spike Glycoprotein, Coronavirus/immunology
• Spike Glycoprotein, Coronavirus/genetics
• SARS-CoV-2/immunology
• COVID-19 Vaccines/immunology
• COVID-19/prevention & control
• COVID-19/immunology
• Mice
• Mice, Transgenic
• Immunity, Humoral
• Antibodies, Viral/immunology
• Antibodies, Viral/blood
• Humans
• Immunity, Cellular
• Angiotensin-Converting Enzyme 2/immunology
• Angiotensin-Converting Enzyme 2/genetics
• Angiotensin-Converting Enzyme 2/metabolism
• Antibodies, Neutralizing/immunology
• Antibodies, Neutralizing/blood
• Female
• Vaccines, DNA/immunology
• Vaccinia virus/immunology
• Vaccinia virus/genetics
• Immunogenicity, Vaccine

• Hepatitis C Virus (HCV)
• T cell
• cellular immunity
• vaccine

• Seed grant Cleveland Clinic

• COVID-19
• MVA-based vaccine
• S protein
• SARS-CoV-2
• efficacy
• immunogenicity
• mice
• variants of concern

• Mice
• Animals
• Humans
• SARS-CoV-2/genetics
• Vaccinia virus/genetics
• COVID-19 Vaccines
• Antibodies, Viral
• COVID-19/prevention & control
• Mice, Inbred C57BL
• Vaccines

• hepatitis C virus
• promising vaccine
• therapeutic strategies

• Animals
• Hepacivirus/genetics
• Antiviral Agents
• Hepatitis C, Chronic
• Hepatitis C/drug therapy
• Hepatitis C/prevention & control
• Vaccines
• RNA, Small Interfering
• Antibodies, Monoclonal
• MicroRNAs

• B and T cell immune responses
• SARS-CoV-2
• binding and neutralizing antibodies
• efficacy
• mice studies
• multi-patch vaccine
• poxvirus MVA

• ISG15
• VACV
• actin tails

• Animals
• Mice
• Vaccinia virus/genetics
• Interferons
• Actins/metabolism
• Proteomics
• Fibroblasts/metabolism
• Viral Proteins/genetics
• Viral Proteins/metabolism
• Virion/genetics

• R35 GM137961 NIGMS NIH HHS
• MEC | Spanish National Plan for Scientific and Technical Research and Innovation and State secretary of R+D and FEDER/FSE

• HIV
• IFN
• ISG15
• Modify Vaccinia virus Ankara
• adjuvant
• inmunity
• vaccine

We generated an optimized COVID-19 vaccine candidate based on the modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein, termed MVA-CoV2-S(3P). The S(3P) protein was expressed at higher levels (2-fold) than the non-stabilized S in cells infected with the corresponding recombinant MVA viruses. One single dose of MVA-CoV2-S(3P) induced higher IgG and neutralizing antibody titers against parental SARS-CoV-2 and variants of concern than MVA-CoV2-S in wild-type C57BL/6 and in transgenic K18-hACE2 mice. In immunized C57BL/6 mice, two doses of MVA-CoV2-S or MVA-CoV2-S(3P) induced similar levels of SARS-CoV-2-specific B- and T-cell immune responses. Remarkably, a single administration of MVA-CoV2-S(3P) protected all K18-hACE2 mice from morbidity and mortality caused by SARS-CoV-2 infection, reducing SARS-CoV-2 viral loads, histopathological lesions, and levels of pro-inflammatory cytokines in the lungs. These results demonstrated that expression of a novel full-length prefusion-stabilized SARS-CoV-2 S protein by the MVA poxvirus vector enhanced immunogenicity and efficacy against SARS-CoV-2 in animal models, further supporting MVA-CoV2-S(3P) as an optimized vaccine candidate for clinical trials.

• MVA vector
• SARS-CoV-2 vaccine
• mouse model
• prefusion-stabilized S protein
• protective efficacy

• E1E2
• HCV
• structure-based vaccine design

• sars-cov-2
• covid-19
• mva
• poxvirus
• vaccines
• s protein
• t cell responses
• neutralizing antibodies
• k18-hace2 mice
• sars-cov-2 vaccine efficacy

• Fondo Supera COVID-19
• Ferrovial
• MEC | Instituto de Salud Carlos III (ISCIII)
• MEC | Consejo Superior de Investigaciones Científicas (CSIC)
• Fundación Mapfre (Mapfre Foundation)
• Fundación Banco Santander (Santander Fundación)

Hepatitis C virus (HCV) represents a major global health challenge and an efficient vaccine is urgently needed. Many HCV vaccination strategies employ recombinant versions of the viral E2 glycoprotein. However, recombinant E2 readily forms disulfide-bonded aggregates that might not be optimally suited for vaccines. Therefore, we have designed an E2 protein in which we strategically changed eight cysteines to alanines (E2.C8A). E2.C8A formed predominantly monomers and virtually no aggregates. Furthermore, E2.C8A also interacted more efficiently with broadly neutralizing antibodies than conventional E2. We used mice to evaluate different prime/boost immunization strategies involving a modified vaccinia virus Ankara (MVA) expressing the nearly full-length genome of HCV (MVA-HCV) in combination with either the E2 aggregates or the E2.C8A monomers. The combined MVA-HCV/E2 aggregates prime/boost strategy markedly enhanced HCV-specific effector memory CD4⁺ T cell responses and antibody levels compared to MVA-HCV/MVA-HCV. Moreover, the aggregated form of E2 induced higher levels of anti-E2 antibodies in vaccinated mice than E2.C8A monomers. These antibodies were cross-reactive and mainly of the IgG1 isotype. Our findings revealed how two E2 viral proteins that differ in their capacity to form aggregates are able to enhance to different extent the HCV-specific cellular and humoral immune responses, either alone or in combination with MVA-HCV. These combined protocols of MVA-HCV/E2 could serve as a basis for the development of a more effective HCV vaccine.

• CD4 and CD8 T cells
• E2 protein
• HCV
• MVA
• antibodies
• cysteines
• disulfide bonds
• immune responses
• mice
• vaccine

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive memory loss and cognitive decline that has been associated with an accumulation in the brain of intracellular neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein, and extracellular senile plaques formed by β-amyloid peptides. Currently, there is no cure for AD and after the failure of anti β-amyloid therapies, active and passive tau immunotherapeutic approaches have been developed in order to prevent, reduce or ideally reverse the disease. Vaccination is one of the most effective approaches to prevent diseases and poxviruses, particularly modified vaccinia virus Ankara (MVA), are one of the most promising viral vectors used as vaccines against several human diseases. Thus, we present here the generation and characterization of the first MVA vectors expressing human tau genes; the full-length 4R2N tau protein or a 3RC tau fragment containing 3 tubulin-binding motifs and the C-terminal region (termed MVA-Tau4R2N and MVA-Tau3RC, respectively). Both MVA-Tau recombinant viruses efficiently expressed the human tau 4R2N or 3RC proteins in cultured cells, being detected in the cytoplasm of infected cells and co-localized with tubulin. These MVA-Tau vaccines impacted the innate immune responses with a differential recruitment of innate immune cells to the peritoneal cavity of infected mice. However, no tau-specific T cell or humoral immune responses were detected in vaccinated mice. Immunization of transgenic P301S mice, a mouse model for tauopathies, with a DNA-Tau prime/MVA-Tau boost approach showed no significant differences in the hyperphosphorylation of tau, motor capacity and survival rate, when compared to non-vaccinated mice. These findings showed that a well-established and potent protocol of T and B cell activation based on DNA/MVA prime/boost regimens using DNA and MVA vectors expressing tau full-length 4R2N or 3RC proteins is not sufficient to trigger tau-specific T and B cell immune responses and to induce a protective effect against tauopathy in this P301S murine model. In the pursuit of AD vaccines, our results highlight the need for novel optimized tau immunogens and additional modes of presentation of tau protein to the immune system.

• Alzheimer
• MVA
• P301S transgenic mice
• pathology
• poxvirus
• tau

There is an urgent need for the development of potent vaccination regimens that are able to induce specific T and B cell responses against human immunodeficiency virus type 1 (HIV-1). Here, we describe the generation and characterization of a fusion antigen comprised of the HIV-1 envelope GP120 glycoprotein from clade C (GP120C) fused at its C-terminus, with the modified vaccinia virus (VACV) 14K protein (A27L gene) (termed GP120C14K). The design is directed toward improving the immunogenicity of the GP120C protein through its oligomerization facilitated by the fused VACV 14K protein that results in hexamer-like structures. Two different immunogens were generated: a recombinant GP120C14K fusion protein (purified from a stable CHO-K1 cell line) and a recombinant modified vaccinia virus Ankara (MVA) poxvirus vector expressing the GP120C14K fusion protein (termed MVA-GP120C14K). The GP120C14K fusion protein is recognized by broadly neutralizing antibodies (bNAbs) against HIV-1. In a murine model, a heterologous prime/boost immunization regimen with MVA-GP120C14K prime followed by adjuvanted GP120C14K protein boost generated stronger and polyfunctional HIV-1 Env-specific CD8 T cell responses when compared with the delivery of the monomeric GP120C form. Furthermore, the immunization protocol MVA-GP120C14K/GP120C14K elicited higher HIV-1 Env-specific T follicular helper cells, germinal center B cells and antibody responses than monomeric GP120. In addition, a similar MVA-GP120C14K prime/GP120C14K protein boost regimen performed in rabbits triggered high HIV-1-Env-specific IgG binding antibody titers that were capable of neutralizing HIV-1 pseudoviruses. The extent of HIV-1 neutralization was comparable to that elicited by the current standard GP140 SOSIP trimers from clades B and C when immunized as MVA-SOSIP prime/SOSIP protein boost regimen. Overall, the novel fusion antigen and the corresponding immunization scheme provided in this report can therefore be considered as potential vaccine strategies against HIV-1.

• CD8 T cells
• GC B cells
• GP120C14K
• HIV-1 neutralizing antibodies
• MVA-HIV vaccine
• SOSIPs
• Tfh cells
• VACV 14K protein

• Bacterial artificial chromosome
• Norovirus
• Recombinant MVA
• Self-excising

• HCV
• MVA
• alphavirus replicon
• immune response
• mice
• poxvirus
• vaccine

The development of an effective Human Immunodeficiency Virus (HIV) vaccine that is able to stimulate both the humoral and cellular HIV-1-specific immune responses remains a major priority challenge. In this study, we described the generation and preclinical evaluation of single and double modified vaccinia virus Ankara (MVA)-based candidates expressing the HIV-1 clade C membrane-bound gp145(ZM96) trimeric protein and/or the Gag(ZM96)-Pol-Nef(CN54) (GPN) polyprotein that was processed to form Gag-induced virus-like particles (VLPs). In vitro characterization of MVA recombinants revealed the stable integration of HIV-1 genes without affecting its replication capacity. In cells that were infected with Env-expressing viruses, the gp145 protein was inserted into the plasma membrane exposing critical epitopes that were recognized by broadly neutralizing antibodies (bNAbs), whereas Gag-induced VLPs were released from cells that were infected with GPN-expressing viruses. VLP particles as well as purified MVA virions contain Env and Gag visualized by immunoelectron microscopy and western-blot of fractions that were obtained after detergent treatments of purified virus particles. In BALB/c mice, homologous MVA-gp145-GPN prime/boost regimen induced broad and polyfunctional Env- and Gag-specific CD4 T cells and antigen-specific T follicular helper (Tfh) and Germinal Center (GC) B cells, which correlated with robust HIV-1-specific humoral responses. Overall, these results support the consideration of MVA-gp145-GPN vector as a potential vaccine candidate against HIV-1.

• CD4 T cells
• Env-gp145
• GC B cells
• Gag-Pol-Nef
• HIV-1
• MVA vaccine
• Tfh
• VLPs
• humoral responses
• immunogenicity

• Hepatitis C virus
• Humanized mice
• Immunization
• Neutralizing antibodies

• Animals
• Antibodies, Neutralizing/immunology
• Antibodies, Neutralizing/therapeutic use
• Disease Models, Animal
• Hepacivirus/immunology
• Hepatitis C/immunology
• Hepatitis C/prevention & control
• Hepatitis C/virology
• Humans
• Immunogenicity, Vaccine
• Liver/cytology
• Liver/immunology
• Liver Transplantation
• Mice
• Mice, Transgenic
• Neutralization Tests/instrumentation
• Neutralization Tests/methods
• Transplantation Chimera
• Treatment Outcome
• Viral Envelope Proteins/immunology
• Viral Hepatitis Vaccines/immunology
• Viral Hepatitis Vaccines/therapeutic use

• R01 AI079031 NIAID NIH HHS
• R01 AI107301 NIAID NIH HHS
• R21 AI117213 NIAID NIH HHS
• T32 GM007388 NIGMS NIH HHS

Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that affects humans and can cause severe neurological complications, including Guillain-Barré syndrome and microcephaly. Since 2007 there have been three large outbreaks; the last and larger spread in the Americas in 2015. Actually, ZIKV is circulating in the Americas, Southeast Asia, and the Pacific Islands, and represents a potential pandemic threat. Given the rapid ZIKV dissemination and the severe neurological and teratogenic sequelae associated with ZIKV infection, the development of a safe and efficacious vaccine is critical. In this study, we have developed and characterized the immunogenicity and efficacy of a novel ZIKV vaccine based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the ZIKV prM and E structural genes (termed MVA-ZIKV). MVA-ZIKV expressed efficiently the ZIKV structural proteins, assembled in virus-like particles (VLPs) and was genetically stable upon nine passages in cell culture. Immunization of mice with MVA-ZIKV elicited antibodies that were able to neutralize ZIKV and induced potent and polyfunctional ZIKV-specific CD8⁺ T cell responses that were mainly of an effector memory phenotype. Moreover, a single dose of MVA-ZIKV reduced significantly the viremia in susceptible immunocompromised mice challenged with live ZIKV. These findings support the use of MVA-ZIKV as a potential vaccine against ZIKV.

An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B protein contained conserved regions from Gag, Pol, and Nef proteins including multiple CD4 and CD8 T cell epitopes functionally associated with HIV control. Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell responses with broader epitope recognition and higher polyfunctional profile than the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations. Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell response was significantly compromised in DNA-TMEP-primed animals. Our results revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and supported the application of these combined vectors in HIV-1 prevention and/or therapy.

• HIV-1
• MVA
• immunogenicity
• multiepitopic vaccine

• AIDS Vaccines/administration & dosage
• AIDS Vaccines/immunology
• Animals
• CD8-Positive T-Lymphocytes/immunology
• Epitopes, T-Lymphocyte/immunology
• Female
• Genetic Vectors
• HIV Antigens/immunology
• HIV Infections/immunology
• HIV Infections/prevention & control
• HIV-1
• Immunization, Secondary
• Immunogenicity, Vaccine
• Mice
• Mice, Inbred BALB C
• Vaccines, DNA/immunology
• Vaccinia virus

• C6L
• HCV
• MVA
• cellular responses
• host gene expression
• humoral responses
• interferon
• mice
• poxvirus
• vaccine

• Ebola
• GP
• MVA
• VP40
• immunogenicity
• mice
• poxvirus
• protection

• blood
• inflammation
• lymph node
• modified virus Ankara
• non-human primate
• skin
• systems biology
• vaccine

Cellular immunological assays are important tools for the monitoring of responses to T-cell-inducing vaccine candidates. As these bioassays are often technically complex and require considerable experience, careful technology transfer between laboratories is critical if high quality, reproducible data that allows comparison between sites, is to be generated. The aim of this study, funded by the European Union Framework Program 7-funded TRANSVAC project, was to optimise Standard Operating Procedures and the technology transfer process to maximise the reproducibility of three bioassays for interferon-gamma responses: enzyme-linked immunosorbent assay (ELISA), ex-vivo enzyme-linked immunospot and intracellular cytokine staining. We found that the initial variability in results generated across three different laboratories reduced following a combination of Standard Operating Procedure harmonisation and the undertaking of side-by-side training sessions in which assay operators performed each assay in the presence of an assay ‘lead’ operator. Mean inter-site coefficients of variance reduced following this training session when compared with the pre-training values, most notably for the ELISA assay. There was a trend for increased inter-site variability at lower response magnitudes for the ELISA and intracellular cytokine staining assays. In conclusion, we recommend that on-site operator training is an essential component of the assay technology transfer process and combined with harmonised Standard Operating Procedures will improve the quality, reproducibility and comparability of data produced across different laboratories. These data may be helpful in ongoing discussions of the potential risk/benefit of centralised immunological assay strategies for large clinical trials versus decentralised units.

• MVA-PfCS
• P. falciparum circumsporozoite
• antibodies
• malaria vaccine
• oligomeric PfCS
• polyfunctional CD8+ T cells
• transgenic P. berghei

• Attenuation
• Brucella abortus
• Live vaccine
• Mouse
• T cells

• C7L
• LACK
• Leishmania
• NYVAC
• Vaccine
• Vaccinia virus

• Animals
• Antigens, Protozoan/genetics
• Antigens, Protozoan/immunology
• Disease Models, Animal
• Female
• Gene Expression
• Genetic Vectors/chemistry
• Genetic Vectors/immunology
• HeLa Cells
• Humans
• Immunization, Secondary
• Interferon-gamma/genetics
• Interferon-gamma/immunology
• Interleukin-2/genetics
• Interleukin-2/immunology
• Leishmania major/drug effects
• Leishmania major/genetics
• Leishmania major/immunology
• Leishmaniasis Vaccines/administration & dosage
• Leishmaniasis Vaccines/biosynthesis
• Leishmaniasis Vaccines/genetics
• Leishmaniasis, Cutaneous/immunology
• Leishmaniasis, Cutaneous/parasitology
• Leishmaniasis, Cutaneous/prevention & control
• Lysosomal Membrane Proteins/genetics
• Lysosomal Membrane Proteins/immunology
• Mice
• Mice, Inbred BALB C
• Protozoan Proteins/genetics
• Protozoan Proteins/immunology
• T-Lymphocytes/drug effects
• T-Lymphocytes/immunology
• T-Lymphocytes/parasitology
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/immunology
• Vaccinia virus/genetics
• Vaccinia virus/immunology
• Viral Proteins/genetics
• Viral Proteins/immunology
• Virus Replication

• Animals
• Antibodies, Neutralizing/immunology
• Antibodies, Viral/immunology
• Cytokines/metabolism
• Disease Models, Animal
• Genetic Vectors/administration & dosage
• Genetic Vectors/genetics
• Herpes Simplex Virus Vaccines/administration & dosage
• Herpesvirus 2, Human/immunology
• Immunoglobulin G/immunology
• Influenza A Virus, H5N1 Subtype/immunology
• Mice
• Vaccination
• Vaccines, DNA
• Vaccinia/metabolism
• Vaccinia/prevention & control
• Vaccinia virus/genetics
• Vaccinia virus/immunology
• Viral Vaccines/administration & dosage
• Viral Vaccines/genetics

After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases.

• Animals
• History, 18th Century
• History, 19th Century
• History, 20th Century
• History, 21st Century
• Humans
• Poxviridae/immunology
• Poxviridae/isolation & purification
• Smallpox/prevention & control
• Smallpox Vaccine/history
• Smallpox Vaccine/immunology
• Smallpox Vaccine/isolation & purification
• Vaccines, Attenuated/history
• Vaccines, Attenuated/immunology
• Vaccines, Attenuated/isolation & purification
• Vaccines, Synthetic/history
• Vaccines, Synthetic/immunology
• Vaccines, Synthetic/isolation & purification

Chikungunya virus (CHIKV) is a re-emerging arbovirus associated with febrile illness often accompanied by rash and arthralgia that may persist for several years. Outbreaks are associated with high morbidity and create a public health challenge for countries affected. Recent outbreaks have occurred in both Europe and the Americas, suggesting CHIKV may continue to spread. Despite the sustained threat of the virus, there is no approved vaccine or antiviral therapy against CHIKV. Therefore, it is critical to develop a vaccine that is both well tolerated and highly protective.

In this study, we describe the construction and characterization of a modified Vaccinia virus Ankara (MVA) virus expressing CHIKV E3 and E2 proteins (MVA-CHIK) that protected several mouse models from challenge with CHIKV. In particular, BALB/c mice were completely protected against viremia upon challenge with CHIKV after two doses of MVA-CHIK. Additionally, A129 mice (deficient in IFNα/β) were protected from viremia, footpad swelling, and mortality. While high anti-virus antibodies were elicited, low or undetectable levels of neutralizing antibodies were produced in both mouse models. However, passive transfer of MVA-CHIK immune serum to naïve mice did not protect against mortality, suggesting that antibodies may not be the main effectors of protection afforded by MVA-CHIK. Furthermore, depletion of CD4⁺, but not CD8⁺ T-cells from vaccinated mice resulted in 100% mortality, implicating the indispensable role of CD4⁺ T-cells in the protection afforded by MVA-CHIK.

The results presented herein demonstrate the potential of MVA to effectively express CHIKV E3-E2 proteins and generate protective immune responses. Our findings challenge the assumption that only neutralizing antibodies are effective in providing protection against CHIKV, and provides a framework for the development of novel, more effective vaccine strategies to combat CHIKV.

Chikungunya virus (CHIKV) has recently re-emerged from Africa to cause disease outbreaks in Asia, Europe, and more recently the Caribbean. The virus is transmitted by Aedes mosquitoes and causes a disease that is characterized by high fever and incapacitating joint pain that can cause great personal and economic loss. At present, no approved vaccine or antivirals are approved against CHIKV. In this study, we developed a novel CHIKV vaccine that is vectored by Modified Vaccinia virus Ankara (MVA), an attenuated vaccine vector which has been shown to be safe in humans and induce a strong immune response. The vaccine expresses the E3 and E2 proteins of CHIKV, the latter of which is thought to be the main mediator of protection. The vaccine was effective in two mouse models and protected against all markers of disease tested despite the absence of high levels of neutralizing antibodies, the gold standard of protection. Depletion of CD4+ T cells from vaccinated mice resulted in loss of protection, implicating these cells in the protection induced by the vaccine.

• Animals
• Antibodies, Viral/blood
• Chikungunya Fever/immunology
• Chikungunya Fever/prevention & control
• Chikungunya Fever/virology
• Chikungunya virus/genetics
• Chikungunya virus/immunology
• Genetic Vectors/genetics
• Mice
• Mice, Inbred BALB C
• Vaccinia virus/genetics
• Vaccinia virus/immunology
• Viral Vaccines/genetics
• Viral Vaccines/immunology

• R01 AI093491 NIAID NIH HHS
• T32 AI007414 NIAID NIH HHS
• #AI093491-02 NIAID NIH HHS

During the course of chronic hepatitis C virus (HCV) infection, various extrahepatic manifestations of autoimmune disorders may occur, including arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid dysfunction. In addition, the prevalence of circulating autoantibodies is high among patients with HCV infection. Commonly detected autoantibodies in HCV-infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection. A possible reason for antibody production is overactivation and proliferation of B lymphocytes, via the interaction with the surface protein of HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided. This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection.

• Hepatitis C virus
• Autoantibody
• Autoimmune
• Biomarker
• Cytokine

• Animals
• Autoantibodies/biosynthesis
• Autoantibodies/blood
• Autoimmune Diseases/blood
• Autoimmune Diseases/etiology
• Biomarkers/blood
• Hepatitis C, Chronic/blood
• Hepatitis C, Chronic/complications
• Hepatitis C, Chronic/immunology
• Humans