Vaccination of mice with plasmids expressing processed capsid protein of foot-and-mouth disease virus—Importance of dominant and subdominant epitopes for antigenicity and protection

Frimann, Tine Holland; Barfoed, Annette Malene; Aasted, Bent; Kamstrup, Søren

doi:10.1016/j.vaccine.2007.06.002

Cited by 15 publications

(10 citation statements)

References 30 publications

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“…The differences in results between these two studies were attributed to either different vaccination approaches (DNA vaccine versus inactivated virus) or the animal species tested (mice versus cattle). However, the use of xenoepitope substitution of the decoy epitope in this work does appear to have broadened immunity to different epitopes found in the native virus (in the peptide group containing the PRRSV substitution), which is in keeping with the results of Frimann et al (16).Two similarities of our study with Frimann et al, which differ from those of Fowler et al, were the animal species used (mice versus cattle) and serotype of FMDV used (type O versus type A). Given the immense variation in G-H loop amino acid sequence between serotypes (with the exception of the RGD integrin-binding motif), it is possible that the region upstream of RGD is not as important for immunity against type A viruses (and may not even contain a decoy epitope).…”

Section: Discussionsupporting

confidence: 86%

“…Capsid-based DNA vaccines bearing full or partial replacement of the G-H loop (including the decoy epitope) with glycine residues have been found to greatly enhance cross-reactivity of sera from inoculated mice to different serotypes of FMDV. Complete replacement of the G-H loop was inefficient at protecting mice from homologous challenge, but partial G-H loop replacement appears to have prevented viremia and death in vaccinated animals (16). In a related experiment, Fowler et al (14) determined that partial loss of the FMDV serotype A G-H loop, immediately upstream of RGD and through the downstream alpha-helix (the structure of which was predicted to be lost by computational analysis), in inactivated vaccines did not generate broadened immunity or immune refocusing in cattle.…”

Section: Discussionmentioning

confidence: 96%

“…However, G-H loop replacement also appears to have generated a humoral response that has increased cross-reactivity with different serotypes (and many escape variants) as well. Complete loss of the G-H loop was not protective when animals were challenged with a lethal dose of homologous virus; however, partial deletion of the G-H loop was protective from challenge (16 ) or a presumably tolerogenic epitope from murine albumin (here, MT). Substituted xenoepitopes were selected based on their immunogenicity, length, and secondary structure, using the wild-type G-H loop as a template.…”

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confidence: 98%

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Xenoepitope Substitution Avoids Deceptive Imprinting and Broadens the Immune Response to Foot-and-Mouth Disease Virus

Szczepanek

Barrette

Rood

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTMany RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as “decoy epitopes,” which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates. A series of chimeric cyclic peptides resembling the type O G-H loop were prepared, each bearing a defined “B cell xenoepitope” from another virus in place of the native decoy epitope. These sequences were derived from porcine respiratory and reproductive syndrome virus (PRRSV), from HIV, or from a presumptively tolerogenic sequence from murine albumin and were subsequently used as immunogens in BALB/c mice. Cross-reactive antibody responses against all peptides were compared to a wild-type peptide and ovalbumin (OVA). A broadened antibody response was generated in animals inoculated with the PRRSV chimeric peptide, in which virus binding of serum antibodies was also observed. A B cell epitope mapping experiment did not reveal recognition of any contiguous linear epitopes, raising the possibility that the refocused response was directed to a conformational epitope. Taken together, these results indicate that xenoepitope substitution is a novel method for immune refocusing against decoy epitopes of RNA viruses such as FMDV as part of the rational design of next-generation vaccines.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 96%

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confidence: 98%

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Xenoepitope Substitution Avoids Deceptive Imprinting and Broadens the Immune Response to Foot-and-Mouth Disease Virus

Szczepanek

Barrette

Rood

et al. 2012

Clin. Vaccine Immunol.

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“…It should be noted that the RGD sequence was deleted from the G-H loop. The three-dimensional and antigenic structures of many different serotypes of the FMDV have been examined [8]. In spite of losing the RGD sequence and acquiring a Asp 26 →Glu substitution in a beta sheet located in a small groove of the 3D pol protein, the virus grew in a BHK-21 suspension cell culture and exerted cytopathic effects after 16~18 h. Since this strain is used as a vaccine strain, it may be inferred that the RGD does not have a key role in the virus binding to cells during infection.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of a 13-amino acid deletion in VP1 (1D) protein and novel amino acid substitutions in 3D polymerase protein of foot and mouth disease virus subtype A/Iran87

et al. 2011

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The nucleotide sequence of the VP1 (1D) and partial 3D polymerase (3Dpol) coding regions of the foot and mouth disease virus (FMDV) vaccine strain A/Iran87, a highly passaged isolate (~150 passages), was determined and aligned with previously published FMDV serotype A sequences. Overall analysis of the amino acid substitutions revealed that the partial 3Dpol coding region contained four amino acid alterations. Amino acid sequence comparison of the VP1 coding region of the field isolates revealed deletions in the highly passaged Iranian isolate (A/Iran87). The prominent G-H loop of the FMDV VP1 protein contains the conserved arginine-glycine-aspartic acid (RGD) tripeptide, which is a well-known ligand for a specific cell surface integrin. Despite losing the RGD sequence of the VP1 protein and an Asp26→Glu substitution in a beta sheet located within a small groove of the 3Dpol protein, the virus grew in BHK 21 suspension cell cultures. Since this strain has been used as a vaccine strain, it may be inferred that the RGD deletion has no critical role in virus attachment to the cell during the initiation of infection. It is probable that this FMDV subtype can utilize other pathways for cell attachment.

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“…The VP1 capsid protein harbors the main neutralizing epitopes of EV71 [21-24] and its sequence variability is used to classify EV71 into subgenogroups [25]. In addition, neutralizing or antigenic epitopes on the VP0 and VP2 proteins have been described in other members of the picornavirus family including poliovirus [26,27], coxsackievirus A9 [28], foot-mouth-disease virus [29], and parechovirus [30]. Furthermore, VP0 has been proposed as a diagnostic tool to detect anti-human parechovirus 1 antibodies in patient sera [31,32].…”

Section: Introductionmentioning

confidence: 99%

Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein

Kiener

Jia

Lim

et al. 2012

Virol J

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BackgroundEnterovirus 71 (EV71) has emerged as a major causative agent of hand, foot and mouth disease in the Asia-Pacific region over the last decade. Hand, foot and mouth disease can be caused by different etiological agents from the enterovirus family, mainly EV71 and coxsackieviruses, which are genetically closely related. Nevertheless, infection with EV71 may occasionally lead to high fever, neurologic complications and the emergence of a rapidly fatal syndrome of pulmonary edema associated with brainstem encephalitis. The rapid progression and high mortality of severe EV71 infection has highlighted the need for EV71-specific diagnostic and therapeutic tools. Monoclonal antibodies are urgently needed to specifically detect EV71 antigens from patient specimens early in the infection process. Furthermore, the elucidation of viral epitopes will contribute to the development of targeted therapeutics and vaccines.ResultsWe have identified the monoclonal antibody 7C7 from a screen of hybridoma cells derived from mice immunized with the EV71-B5 strain. The linear epitope of 7C7 was mapped to amino acids 142-146 (EDSHP) of the VP2 capsid protein and was characterized in detail. Mutational analysis of the epitope showed that the aspartic acid to asparagine mutation of the EV71 subgenogroup A (BrCr strain) did not interfere with antibody recognition. In contrast, the serine to threonine mutation at position 144 of VP2, present in recently emerged EV71-C4 China strains, abolished antigenicity. Mice injected with this virus strain did not produce any antibodies against the VP2 protein. Immunofluorescence and Western blotting confirmed that 7C7 specifically recognized EV71 subgenogroups and did not cross-react to Coxsackieviruses 4, 6, 10, and 16. 7C7 was successfully used as a detection antibody in an antigen-capture ELISA assay.ConclusionsDetailed mapping showed that the VP2 protein of Enterovirus 71 contains a single, linear, non-neutralizing epitope, spanning amino acids 142-146 which are located in the VP2 protein's E-F loop. The S/T(144) mutation in this epitope confers a loss of VP2 antigenicity to some newly emerged EV71-C4 strains from China. The corresponding monoclonal antibody 7C7 was used successfully in an AC-ELISA and did not cross-react to coxsackieviruses 4, 6, 10, and 16 in immunofluorescence assay and Western blots. 7C7 is the first monoclonal antibody described, that can differentiate Coxsackievirus 16 from Enterovirus 71.

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Vaccination of mice with plasmids expressing processed capsid protein of foot-and-mouth disease virus—Importance of dominant and subdominant epitopes for antigenicity and protection

Cited by 15 publications

References 30 publications

Xenoepitope Substitution Avoids Deceptive Imprinting and Broadens the Immune Response to Foot-and-Mouth Disease Virus

Xenoepitope Substitution Avoids Deceptive Imprinting and Broadens the Immune Response to Foot-and-Mouth Disease Virus

Molecular characterization of a 13-amino acid deletion in VP1 (1D) protein and novel amino acid substitutions in 3D polymerase protein of foot and mouth disease virus subtype A/Iran87

Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein

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