scholarly journals Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape

2021 ◽  
Vol 9 (5) ◽  
pp. 899
Author(s):  
Anthony Torres-Ruesta ◽  
Rhonda Sin-Ling Chee ◽  
Lisa F.P. Ng
Keyword(s):  
Diagnostic Tests ◽  
Inflammatory Arthritis ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Chikv Infection ◽  
Wide Range ◽  
Susceptible Populations ◽  
Humoral Responses

Alphaviruses are mosquito-borne pathogens distributed worldwide in tropical and temperate areas causing a wide range of symptoms ranging from inflammatory arthritis-like manifestations to the induction of encephalitis in humans. Historically, large outbreaks in susceptible populations have been recorded followed by the development of protective long-lasting antibody responses suggesting a potential advantageous role for a vaccine. Although the current understanding of alphavirus antibody-mediated immunity has been mainly gathered in natural and experimental settings of chikungunya virus (CHIKV) infection, little is known about the humoral responses triggered by other emerging alphaviruses. This knowledge is needed to improve serology-based diagnostic tests and the development of highly effective cross-protective vaccines. Here, we review the role of antibody-mediated immunity upon arthritogenic and neurotropic alphavirus infections, and the current research efforts for the development of vaccines as a tool to control future alphavirus outbreaks.

scholarly journals A functional spleen contributes to afucosylated IgG in humans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Immune Cell ◽  
Lymphoid Organ ◽  
Immune Effector ◽  
Adaptive Immune ◽  
Wide Range ◽  
Humoral Responses ◽  
First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

scholarly journals Overproduction of IL-6 and Type-I IFN in a Lethal Case of Chikungunya Virus Infection in an Elderly Man During the 2017 Italian Outbreak

2018 ◽  
Vol 5 (11) ◽  
Author(s):  
Francesca Colavita ◽  
Serena Vita ◽  
Eleonora Lalle ◽  
Fabrizio Carletti ◽  
Licia Bordi ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Strong Increase ◽  
Type I ◽  
Type I Ifn ◽  
Chikv Infection ◽  
Clinical Presentations ◽  
Abnormal Pattern ◽  
Disease Analysis

Abstract Chikungunya fever is caused by Chikungunya virus (CHIKV) and is generally considered a self-limiting disease. However, severe clinical presentations with a high mortality rate have been reported in association with underlying medical conditions. This study reports the molecular characterization of the virus and an abnormal pattern of circulating cytokines in a unique lethal CHIKV case during the 2017 outbreak in Italy, which involved an elderly patient with underlying cardiac disease. Analysis of inflammatory cytokines revealed a strong increase of interferon (IFN)-α and IFN-β, as well as interleukin-6, suggesting a possible role of type-I IFN in the cytokine storm, which may be correlated with unfavorable prognosis of CHIKV infection.

Analysis of antibody response (IgM, IgG, IgG3) to Chikungunya virus using panel of peptides derived from envelope protein for serodiagnosis

2014 ◽  
Vol 52 (2) ◽  
Author(s):  
Priyanka Verma ◽  
Santwana Bhatnagar ◽  
Pradeep Kumar ◽  
Vinita Chattree ◽  
M.M. Parida ◽  
...  
Keyword(s):  
Antibody Response ◽  
Envelope Protein ◽  
Chikungunya Virus ◽  
Humoral Response ◽  
Protective Role ◽  
Diagnostic Purpose ◽  
Chikv Infection ◽  
Insight Into ◽  
Immunodominant Epitopes

AbstractMany epidemic outbreaks of Chikungunya fever (CHIKF) have been reported throughout the world including India after its reemergence in 2005. The immuno protective role of envelope proteins during Chikungunya virus (CHIKV) infection has been reported. With the aim of identifying the immunodominant epitopes within the envelope protein we investigated the detailed analysis of fine specificity of antibody response in different individuals during CHIKV infection.The peptides corresponding to the full length of E1, E2 and E3 proteins of S27 strain of CHIKV were synthesized and their seroreactivity with CHIKV positive patients’ sera collected from different epidemic regions of India was determined using indirect ELISA.The data analysis reveals many potent epitopes throughout the length of envelope E2 protein thus displaying it as the most promising antigen for diagnostic purpose. We found that the main IgG isotype response to envelope protein was predominantly of subclass IgG3. Interestingly, most of the epitopes were found to be conserved for detecting IgM, IgG and IgG3 antibody response.Peptides E2P3, E2P7, E2P16 and E2P17 were revealed as the most immunodominant peptides that together can form the basis for designing an accurate, economical and easy to synthesize a peptide-based immunodiagnostic for CHIKV. This study provides new and important insight into the humoral response generated by CHIKV S27 strain during the early phase of infection.

scholarly journals A Review of Chikungunya Virus-induced Arthralgia: Clinical Manifestations, Therapeutics, and Pathogenesis

2016 ◽  
Vol 10 (1) ◽  
pp. 129-140 ◽  
Author(s):  
Brad A. Goupil ◽  
Christopher N. Mores
Keyword(s):  
Clinical Research ◽  
Chikungunya Virus ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Western Hemisphere ◽  
Joint Disease ◽  
Chikv Infection ◽  
Initial Infection ◽  
Current State

Background:Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that circulates predominantly in tropical and subtropical regions, potentially affecting over 1 billion people. Recently, an outbreak began in the western hemisphere and has resulted in over 1.8 million reported suspected cases. Infection often results in severe fever, rash and debilitating polyarthralgia lasting weeks to months. Additionally, the current literature reports that CHIKV can result in a severe chronic arthralgia and/or arthritis that can last months to years following the initial infection.Objective:The purpose of this review is to evaluate the literature and summarize the current state of knowledge regarding CHIKV-associated disease, including clinical presentation, diagnosis, risk factors for development of severe disease, treatment, and pathogenesis in human patients. Additionally, recommendations are presented regarding avenues for clinical research to help further elucidate the pathogenesis of joint disease associated with CHIKV infection.Conclusion:While there is an association between initial CHIKV infection and acute disease, a causal relationship with development of chronic arthralgia has not been established at this time. Potential causes of chronic CHIKV-induced arthritis have been postulated, including viral persistence, induction of autoimmune disease, and exacerbation of pre-existing joint disease. While there are numerous reports of chronic CHIKV-associated arthralgia and/or arthritis, there is currently no evidence of a definitive link between initial infection and development of chronic disease. Additional, prospective clinical research on CHIKV-associated disease is necessary to further determine the potential role of virus and development of chronic joint disease.

scholarly journals NAP1L1 and NAP1L4 binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein is bivalent and requires phosphorylation

2021 ◽  
Author(s):  
Francisco Dominguez ◽  
Nikita Shiliaev ◽  
Tetyana Lukash ◽  
Peter Agback ◽  
Oksana Palchevska ◽  
...  
Keyword(s):  
Viral Replication ◽  
Chikungunya Virus ◽  
Family Members ◽  
Host Factors ◽  
Nonstructural Proteins ◽  
Host Proteins ◽  
Chikv Infection ◽  
Binding Motifs ◽  
Specific Host ◽  
Wide Range

Chikungunya virus (CHIKV) is one of the most pathogenic members of the Alphavirus genus in the Togaviridae family. Within the last two decades, CHIKV has expanded its presence to both hemispheres and is currently circulating in both Old and New Worlds. Despite the severity and persistence of the arthritis it causes in humans, no approved vaccines or therapeutic means have been developed for CHIKV infection. Replication of alphaviruses, including CHIKV, is determined not only by their nonstructural proteins, but also by a wide range of host factors, which are indispensable components of viral replication complexes (vRCs). Alphavirus nsP3s contain hypervariable domains (HVDs), which encode multiple motifs that drive recruitment of cell- and virus-specific host proteins into vRCs. Our previous data suggested that NAP1 family members are a group of host factors that may interact with CHIKV nsP3 HVD. In this study, we performed a detailed investigation of the NAP1 function in CHIKV replication in vertebrate cells. Our data demonstrate that i) the NAP1-HVD interactions have strong stimulatory effects on CHIKV replication; ii) both NAP1L1 and NAP1L4 interact with the CHIKV HVD; iii) NAP1 family members interact with two motifs, which are located upstream and downstream of the G3BP-binding motifs of CHIKV HVD; iv) NAP1 proteins interact only with a phosphorylated form of CHIKV HVD and HVD phosphorylation is mediated by CK2 kinase; v) NAP1 and other families of host factors redundantly promote CHIKV replication and their bindings have additive stimulatory effects on viral replication.

scholarly journals The native European Aedes geniculatus mosquito species can transmit Chikungunya virus

2019 ◽  
Author(s):  
Jorian Prudhomme ◽  
Albin Fontaine ◽  
Guillaume Lacour ◽  
Jean-Charles Gantier ◽  
Laure Diancourt ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Vector Competence ◽  
Mosquito Species ◽  
Cumulative Distribution ◽  
Mosquito Vector ◽  
Indigenous Species ◽  
Chikv Infection ◽  
Invasive Mosquito ◽  
Virus Emergence

AbstractEurope is the world’s leading tourism destination and is receiving every year travelers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector Aedes albopictus. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of Ae. geniculatus, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with Ae. albopictus.We revealed that Ae. geniculatus was highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in Ae. geniculatus was delayed by several days as compared to Ae. albopictus.Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.Sentence summaryThe European mosquito Aedes geniculatus is highly susceptible to CHIKV infection but disseminate and transmit the virus several days later than Ae. albopictus.

scholarly journals Expanding Regulatory T Cells Alleviates Chikungunya Virus-Induced Pathology in Mice

2015 ◽  
Vol 89 (15) ◽  
pp. 7893-7904 ◽  
Author(s):  
Wendy W. L. Lee ◽  
Teck-Hui Teo ◽  
Zhisheng Her ◽  
Fok-Moon Lum ◽  
Yiu-Wing Kam ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Chikungunya Virus ◽  
Interleukin 2 ◽  
Joint Inflammation ◽  
Chikv Infection ◽  
Joint Pathology ◽  
Alternative Approach ◽  
Control Virus

ABSTRACTChikungunya virus (CHIKV) infection is a reemerging pandemic human arboviral disease. CD4+T cells were previously shown to contribute to joint inflammation in the course of CHIKV infection in mice. The JES6-1 anti-IL-2 antibody selectively expands mouse regulatory T cells (Tregs) by forming a complex with IL-2. In this study, we show that the IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology. It does so by inhibiting the infiltration of CD4+T cells due to the induction of anergy in CHIKV-specific CD4+effector T cells. These findings suggest that activation of Tregs could also become an alternative approach to control CHIKV-mediated disease.IMPORTANCEChikungunya virus (CHIKV) has reemerged as a pathogen of global significance. Patients infected with CHIKV suffer from incapacitating joint pain that severely affects their daily functioning. Despite the best efforts, treatment is still inadequate. While T cell-mediated immunopathology in CHIKV infections has been reported, the role of regulatory T cells (Tregs) has not been explored. The JES6-1 anti-interleukin 2 (IL-2) antibody has been demonstrated to selectively expand mouse Tregs by forming a complex with IL-2. We reveal here that IL-2 JES6-1-mediated expansion of Tregs ameliorates CHIKV-induced joint pathology in mice by neutralizing virus-specific CD4+effector T (Teff) cells. We show that this treatment abrogates the infiltration of pathogenic CD4+T cells through induction of anergy in CHIKV-specific CD4+Teff cells. This is the first evidence where the role of Tregs is demonstrated in CHIKV pathogenesis, and its expansion could control virus-mediated immunopathology.

scholarly journals 116. Role of Maternal Antibodies in Protection Against Postnatal Cytomegalovirus Acquisition

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S4-S4
Author(s):  
Frances Saccoccio ◽  
Hannah Itell ◽  
Skukhang Li ◽  
Jennifer Jenks ◽  
Guan Xie ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Natural Infection ◽  
The United States ◽  
Immune Correlates ◽  
Perinatal Hiv ◽  
Igg Binding ◽  
Maternal Hiv ◽  
Specific Igg ◽  
Humoral Responses

Abstract Background Congenital cytomegalovirus (CMV) is the leading infectious cause of birth defects in the United States. Development of an effective CMV vaccine is a public health priority. However, CMV vaccine development is limited by a poor understanding of the immune correlates of protection, including the role of CMV-specific IgG. Defining the role of passively acquired maternal IgG in the protection of half of the CMV-exposed, breastfeeding infants against postnatal CMV acquisition may inform CMV vaccine design Methods We analyzed CMV-specific humoral responses in 29 CMV-seropositive Ugandan mother–infant pairs. Seventeen mothers were HIV co-infected. Infants were followed weekly for postnatal CMV acquisition using saliva PCR. Twelve infants acquired CMV and 17 infants did not acquire CMV in the first 6 months of life. We compared CMV-specific IgG responses at delivery of mothers whose infants acquired CMV to mothers whose infants did not acquire CMV by 6 months of life and in the infants at 6 weeks of life. We also compared CMV-specific responses in mothers at delivery and infants at 6 weeks of life based on maternal HIV status. Results We found similar CMV-specific total IgG and IgG3 binding, avidity index, neutralization, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity responses in mothers whose infants did or did not acquire CMV by 6 months of life. Moreover, similar CMV-specific IgG binding and neutralization responses were also found between infants who did or did not acquire CMV by 6 months of life. Finally, CMV-specific IgG responses were similar in HIV-infected and uninfected mothers at delivery and in infants at 6 weeks of life regardless of perinatal HIV exposure. Conclusion CMV-binding and functional IgG responses do not appear to impact infant susceptibility to postnatal CMV acquisition in the first 6 months of life, and therefore other viral or immunologic factors contribute to the inefficiency of this mode of CMV transmission. Thus, to provide sterilizing protection against mucosal CMV acquisition, an antibody-based CMV vaccine would likely have to induce higher magnitude or qualitatively different responses than that of natural infection. Disclosures All authors: No reported disclosures.

scholarly journals Evaluation of DNA-Launched Virus-Like Particle Vaccines in an Immune Competent Mouse Model of Chikungunya Virus Infection

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 345
Author(s):  
Jonathan O. Rayner ◽  
Jin Hyun Kim ◽  
Rosemary W. Roberts ◽  
Raphael Ryan Wood ◽  
Brian Fouty ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Vaccine Development ◽  
Immunocompetent Mouse ◽  
Chikv Infection ◽  
Male And Female ◽  
Preclinical Evaluation ◽  
Virus Like Particle ◽  
The World ◽  
Immunocompetent Mice ◽  
Immune Competent Mouse

Chikungunya virus (CHIKV) infection can result in chronic and debilitating arthralgia affecting humans in tropical and subtropical regions around the world, yet there are no licensed vaccines to prevent infection. DNA launched virus like particle (VLP) vaccines represent a potentially safer alternative to traditional live-attenuated vaccines; however, fully characterized immunocompetent mouse models which appropriately include both male and female animals for preclinical evaluation of these, and other, vaccine platforms are lacking. Utilizing virus stocks engineered to express mutations reported to enhance CHIKV virulence in mice, infection of male and female immunocompetent mice was evaluated, and the resulting model utilized to assess the efficacy of candidate DNA launched CHIKV VLP vaccines. Results demonstrate the potential utility of DNA launched VLP vaccines in comparison to a live attenuated CHIKV vaccine and identify gender differences in viral RNA loads that impact interpretation of vaccine efficacy and may have important implications for future CHIKV vaccine development.

scholarly journals MK2a inhibitor CMPD1 abrogates chikungunya virus infection by modulating actin remodeling pathway

2021 ◽  
Author(s):  
Soma Chattopadhyay ◽  
Prabhudutta Mamidi ◽  
Tapas Kumar Nayak ◽  
Abhishek Kumar ◽  
Sameer Kumar ◽  
...  
Keyword(s):  
Viral Infection ◽  
Gene Silencing ◽  
Chikungunya Virus ◽  
Late Phase ◽  
Health Concern ◽  
Chikv Infection ◽  
Viral Copy Number

Chikungunya virus (CHIKV) epidemics around the world have created public health concern with the unavailability of effective drugs and vaccines. This emphasizes the need for molecular understanding of host-virus interactions for developing effective targeted antivirals. Microarray analysis was carried out using CHIKV strain (Prototype and Indian) infected Vero cells and two host isozymes, MK2 and MK3 were selected for further analysis. Gene silencing and drug treatment were performed in vitro and in vivo to unravel the role of MK2/MK3 in CHIKV infection. Gene silencing of MK2 and MK3 abrogated around 58% CHIKV progeny release from the host cell and a MK2 activation (a) inhibitor (CMPD1) treatment demonstrated 68% inhibition of viral infection suggesting a major role of MAPKAPKs during the late phase of CHIKV infection in vitro. Further, it was observed that the inhibition in viral infection is primarily due to the abrogation of lamellipodium formation through modulation of factors involved in the actin cytoskeleton remodeling pathway that is responsible for releasing the virus from the infected cells.  Moreover, CHIKV-infected C57BL/6 mice demonstrated reduction in the viral copy number, lessened disease score and better survivability after CMPD1 treatment. In addition, reduction in expression of key pro-inflammatory mediators such as CXCL13, RAGE, FGF, MMP9 and increase in HGF (a CHIKV infection recovery marker) was observed indicating the effectiveness of this drug against CHIKV. Additionally, CMPD1 also inhibited HSV1 and SARS CoV2-19 infection in vitro. Taken together it can be proposed that MK2 and MK3 are crucial host factors for CHIKV infection and can be considered as key targets for developing effective anti-CHIKV strategies in future.

Sign in / Sign up

Export Citation Format

Share Document