Guinea pig protection test as indicator of potency of oil emulsion foot-and-mouth disease vaccines

AbstractCurrent foot-and-mouth disease (FMD) vaccines have significant limitations, including side effects due to oil emulsions at the vaccination site, a narrow spectrum of protective efficacy, and incomplete host defenses mediated by humoral immunity alone. To overcome these limitations, new FMD vaccines must ensure improved safety with non-oil-based adjuvants, a broad spectrum of host defenses within/between serotypes, and the simultaneous induction of cellular and humoral immunity. We designed a novel, immune-potent, recombinant protein rpHSP70-AD that induces robust cellular immunity and elicits a broad spectrum of host defenses against FMD virus (FMDV) infections. We demonstrated that an oil emulsion-free vaccine containing rpHSP70-AD mediates early, mid-term, and long-term immunity and drives potent host protection against FMDV type O and A, suggesting its potential as an FMD vaccine adjuvant in mice and pigs. These results suggest a key strategy for establishing next-generation FMD vaccines, including novel adjuvants.

Download Full-text

Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

Journal of General Virology ◽

10.1099/vir.0.060939-0 ◽

2014 ◽

Vol 95 (5) ◽

pp. 1104-1116 ◽

Cited By ~ 19

Author(s):

Amin S. Asfor ◽

Sasmita Upadhyaya ◽

Nick J. Knowles ◽

Donald P. King ◽

David J. Paton ◽

...

Keyword(s):

Amino Acid ◽

Guinea Pig ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Amino Acid Residues ◽

Serotype O ◽

Antigenic Sites ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

Download Full-text

Response of young pigs to foot-and-mouth disease oil emulsion vaccination in the presence and absence of maternally derived neutralising antibodies

Research in Veterinary Science ◽

10.1016/s0034-5288(18)30568-x ◽

1986 ◽

Vol 41 (1) ◽

pp. 33-39 ◽

Cited By ~ 18

Author(s):

M.J. FRANCIS ◽

L. BLACK

Keyword(s):

Foot And Mouth Disease ◽

Mouth Disease ◽

Neutralising Antibodies ◽

Oil Emulsion ◽

Young Pigs ◽

Foot And Mouth ◽

Presence And Absence

Download Full-text

Potential allergens in oil emulsion foot-and-mouth disease vaccines for pigs

Epidemiology and Infection ◽

10.1017/s0950268800054431 ◽

1988 ◽

Vol 101 (2) ◽

pp. 477-480 ◽

Cited By ~ 2

Author(s):

L. Black ◽

M. J Francis

Keyword(s):

Foot And Mouth Disease ◽

Mouth Disease ◽

Oil Emulsion ◽

Foot And Mouth

Reactions so far reported after the use of oil emulsion (OE) foot-and-mouth disease (FMD) vaccines in pigs have been infrequent and quick to resolve themselves. Although tentatively ascribed to anaphylaxis, these reactions have received little attention and their mechanism of causation has not been established conclusively.

Download Full-text

Stabilizing effects of excipients on dissociation of intact (146S) foot-and-mouth disease virions into 12S particles during storage as oil-emulsion vaccine

Vaccine ◽

10.1016/j.vaccine.2015.03.066 ◽

2015 ◽

Vol 33 (21) ◽

pp. 2477-2484 ◽

Cited By ~ 11

Author(s):

M.M. Harmsen ◽

H.P.D. Fijten ◽

D.F. Westra ◽

A. Dekker

Keyword(s):

Foot And Mouth Disease ◽

Mouth Disease ◽

Oil Emulsion ◽

Foot And Mouth

Download Full-text

The specific detection of foot-and-mouth disease virus whole particle antigen (140S) by enzyme labelled immunosorbent assay

Journal of Hygiene ◽

10.1017/s0022172400025894 ◽

1979 ◽

Vol 83 (1) ◽

pp. 127-134 ◽

Cited By ~ 18

Author(s):

E. M. E. Abu Elzein ◽

J. R. Crowther

Keyword(s):

Guinea Pig ◽

Disease Virus ◽

Immunosorbent Assay ◽

Solid Phase ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Specific Detection ◽

Sandwich Technique ◽

Mouth Disease Virus ◽

Foot And Mouth

SUMMARYA solid-phase micro-enzyme-labelled immunosorbent assay (ELISA) using guinea pig antiserum against purified (140S) inactivated foot-and-mouth disease (FMD) virus has been usedin a sandwich technique to specifically measure 140S virus in the presence of 12S material.

Download Full-text