The immune response to a recombinant Lactococcus lactis oral vaccine against foot-and-mouth disease virus in mice

ABSTRACT Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves CD3+ CD4− CD8+/−, CD3+ CD4− CD8+Tc, and CD3+ CD4+ CD8+ memory Th but not CD3+ CD4+ CD8− naïve Th lymphocytes. In addition, a profound depletion of the vast majority of peripheral T cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion. Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV.

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Immune response of calves to foot-and-mouth disease virus vaccine emulsified with oil adjuvant. Strategies of vaccination

Vaccine ◽

10.1016/0264-410x(95)00009-p ◽

1995 ◽

Vol 13 (10) ◽

pp. 909-914 ◽

Cited By ~ 17

Author(s):

E.J.A. Späth ◽

E. Smitsaart ◽

A.P.E. Casaro ◽

N. Fondevila ◽

F. Fernández ◽

...

Keyword(s):

Immune Response ◽

Disease Virus ◽

Virus Vaccine ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Mouth Disease Virus ◽

Foot And Mouth

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Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

BMC Veterinary Research ◽

10.1186/s12917-016-0838-x ◽

2016 ◽

Vol 12 (1) ◽

Cited By ~ 16

Author(s):

Michael Eschbaumer ◽

Carolina Stenfeldt ◽

Steven I. Rekant ◽

Juan M. Pacheco ◽

Ethan J. Hartwig ◽

...

Keyword(s):

Immune Response ◽

Virus Infection ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Systemic Immune Response ◽

Virus Persistence ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

Vectored Vaccine

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00035-12 ◽

2012 ◽

Vol 19 (4) ◽

pp. 461-467 ◽

Cited By ~ 5

Author(s):

Steven M. Szczepanek ◽

Roger W. Barrette ◽

Debra Rood ◽

Diana Alejo ◽

Lawrence K. Silbart

Keyword(s):

Immune Response ◽

B Cell ◽

Disease Virus ◽

Rational Design ◽

Rna Viruses ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

Decoy Epitope

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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