scholarly journals The Early Protective Thymus-Independent Antibody Response to Foot-and-Mouth Disease Virus Is Mediated by Splenic CD9+ B Lymphocytes

2007 ◽  
Vol 81 (17) ◽  
pp. 9357-9367 ◽  
Author(s):  
Matias Ostrowski ◽  
Monica Vermeulen ◽  
Osvaldo Zabal ◽  
Patricia I. Zamorano ◽  
Ana M. Sadir ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Lymphocytes ◽  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Immunoglobulin M ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Infection of mice with cytopathic foot-and-mouth disease virus (FMDV) induces a rapid and specific thymus-independent (TI) neutralizing antibody response that promptly clears the virus. Herein, it is shown that FMDV-infected dendritic cells (DCs) directly stimulate splenic innate-like CD9+ B lymphocytes to rapidly (3 days) produce neutralizing anti-FMDV immunoglobulin M antibodies without T-lymphocyte collaboration. In contrast, neither follicular (CD9−) B lymphocytes from the spleen nor B lymphocytes from lymph nodes efficiently respond to stimulation with FMDV-infected DCs. The production of these protective neutralizing antibodies is dependent on DC-derived interleukin-6 (IL-6) and on CD9+ cell-derived IL-10 secretion. In comparison, DCs loaded with UV-inactivated FMDV are significantly less efficient in directly stimulating B lymphocytes to secrete TI antibodies. A critical role of the spleen in the early production of anti-FMDV antibodies in infected mice was also demonstrated in vivo. Indeed, either splenectomy or functional disruption of the marginal zone of the spleen delays and reduces the magnitude of the TI anti-FMDV antibody response in infected mice. Together, these results indicate that in addition to virus localization, the FMDV-mediated modulation of DC functionality is a key parameter that collaborates in the induction of a rapid and protective TI antibody response against this virus.

scholarly journals Insertion of type O-conserved neutralizing epitope into the foot-and-mouth disease virus type Asia1 VP1 G-H loop: effect on viral replication and neutralization phenotype

2012 ◽  
Vol 93 (7) ◽  
pp. 1442-1448 ◽  
Author(s):  
Haiwei Wang ◽  
Mei Xue ◽  
Decheng Yang ◽  
Guohui Zhou ◽  
Donglai Wu ◽  
...  
Keyword(s):  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Neutralizing Epitope ◽  
Fmdv Serotypes ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Type ◽  
Neutralizing Epitopes

Previously, we finely mapped the neutralizing epitopes recognized by foot-and-mouth disease virus (FMDV) type Asia1-specific mAb 3E11 and FMDV type O-specific mAb 8E8. In this study, we engineered recombinant FMDVs of the serotype Asia1 (rFMDVs) displaying the type O-neutralizing epitope recognized by the mAb 8E8. These epitope-inserted viruses were genetically stable and exhibited growth properties that were similar to those of their parental virus. Importantly, the recombinant virus rFMDV-C showed neutralization sensitivity to both FMDV type Asia1 and type O mAbs, as well as to polyclonal antibodies. These results indicated that this epitope-inserted virus has the potential to induce neutralizing antibodies against both FMDV type Asia1 and type O. Our results demonstrated that the G-H loop of FMDV type Asia1 effectively displays the protective neutralizing epitopes of other FMDV serotypes, making this an attractive approach for the design of novel FMDV vaccines.

scholarly journals Intranasal Immunization of Guinea Pigs with an Immunodominant Foot-and-Mouth Disease Virus Peptide Conjugate Induces Mucosal and Humoral Antibodies and Protection against Challenge

2003 ◽  
Vol 77 (13) ◽  
pp. 7486-7491 ◽  
Author(s):  
D. Fischer ◽  
D. Rood ◽  
R. W. Barrette ◽  
A. Zuwallack ◽  
E. Kramer ◽  
...  
Keyword(s):  
Disease Virus ◽  
Guinea Pigs ◽  
Neutralizing Antibodies ◽  
Immunoglobulin A ◽  
Foot And Mouth Disease ◽  
Keyhole Limpet Hemocyanin ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Nasal Secretions

ABSTRACT Guinea pigs immunized intranasally with a keyhole limpet hemocyanin-linked peptide, corresponding to the prominent G-H loop of the VP1 protein of foot-and-mouth disease virus, raised substantial levels of antipeptide and virus-neutralizing antibodies in sera and of peptide-specific secretory immunoglobulin A in nasal secretions. In groups of animals immunized intranasally without adjuvant, 86 percent were fully protected upon challenge with homotypic virus. Surprisingly, animals given the peptide conjugates plus the mucosal adjuvant cholera toxin were afforded only partial protection in that primary lesions were observed in most animals, although spread to other feet was prevented. These results indicate that intranasal inoculation with the peptide offers a potential route of vaccination against foot-and-mouth disease and may be useful for eliciting protection in the upper respiratory tracts of susceptible animals.

Structures of foot-and-mouth disease virus with bovine neutralizing antibodies reveal the determinant of intra-serotype cross-neutralization

2021 ◽  
Author(s):  
Yong He ◽  
Kun Li ◽  
Li Wang ◽  
Zixian Sun ◽  
Yimei Cao ◽  
...  
Keyword(s):  
Amino Acid ◽  
Disease Virus ◽  
Neutralizing Antibodies ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Threefold Axis ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Bovine Antibody ◽  
Neutralizing Epitopes

Foot-and-mouth disease virus (FMDV) exhibits broad antigenic diversity with poor intra-serotype cross-neutralizing activity. Studies of the determinant involved in this diversity are essential for the development of broadly protective vaccines. In this work, we isolated a bovine antibody, designated R55, that displays cross-reaction with both FMDV A/AF/72 (hereafter named FMDV-AAF) and FMDV A/WH/09 (hereafter named FMDV-AWH) but only has a neutralizing effect on FMDV-AWH. Near-atomic resolution structures of FMDV-AAF-R55 and FMDV-AWH-R55 show that R55 engages the capsids of both FMDV-AAF and FMDV-AWH near the icosahedral threefold axis and binds to the βB and BC/HI-loops of VP2 and to the B-B knob of VP3. The common interaction residues are highly conserved, which is the major determinant for cross-reaction with both FMDV-AAF and FMDV-AWH. In addition, the cryo-EM structure of the FMDV-AWH-R55 complex also shows that R55 binds to VP3 E70 located at the VP3 BC-loop in an adjacent pentamer, which enhances the acid and thermal stabilities of the viral capsid. This may prevent capsid dissociation and genome release into host cells, eventually leading to neutralization of the viral infection. In contrast, R55 binds only to the FMDV-AAF capsid within one pentamer due to the VP3 E70G variation, which neither enhances capsid stability nor neutralizes FMDV-AAF infection. The VP3 E70G mutation is the major determinant involved in the neutralizing differences between FMDV-AWH and FMDV-AAF. The crucial amino acid VP3 E70 is a key component of the neutralizing epitopes, which may aid in the development of broadly protective vaccines. Importance Foot-and-mouth disease virus (FMDV) causes a highly contagious and economically devastating disease in cloven-hoofed animals, and neutralizing antibodies play critical roles in the defense against viral infections. Here, we isolated a bovine antibody (R55) using the single B cell antibody isolation technique. Enzyme-linked immunosorbent assays (ELISA) and virus neutralization tests (VNT) showed that R55 displays cross-reactions with both FMDV-AWH and FMDV-AAF but only has a neutralizing effect on FMDV-AWH. Cryo-EM structures, fluorescence-based thermal stability assays and acid stability assays showed that R55 engages the capsid of FMDV-AWH near the icosahedral threefold axis and informs an interpentamer epitope, which overstabilizes virions to hinder capsid dissociation to release the genome, eventually leading to neutralization of viral infection. The crucial amino acid VP3 E70 forms a key component of neutralizing epitopes, and the determination of the VP3 E70G mutation involved in the neutralizing differences between FMDV-AWH and FMDV-AAF could aid in the development of broadly protective vaccines.

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