JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL

Immune responses and protection by vaccine and various vaccine adjuvant candidates to virulent porcine reproductive and respiratory syndrome virus

Wasin Charerntantanakul, Ratree Platt, Wesley Johnson, Michael Roof, Eric Vaughn, James A Roth
Veterinary Immunology and Immunopathology 2006 January 15, 109 (1): 99-115
16165219
Various vaccine adjuvant candidates were assessed with the modified-live porcine reproductive and respiratory syndrome virus (MLV PRRSV) (Ingelvac PRRS MLV) vaccine. Their influence on humoral-mediated immune (HMI) and cell-mediated immune (CMI) responses as well as protection from virulent PRRSV challenge (MN-184) was evaluated. Ninety seronegative pigs were randomly divided into nine groups of 10 pigs. One group received MLV vaccine alone. Five groups received MLV vaccine with either bacterial endotoxin-derived adjuvant (ET), mixed open reading frame 5 (ORF5) peptides derived from various PRRSV isolates, porcine interferon alpha (IFNalpha), polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), or porcine interleukin-12 (IL-12). One group did not receive MLV vaccine but was immunized with ORF5 peptides conjugated with cholera toxin (ORF5 peptide/CT). Two groups served as challenged and unchallenged non-vaccinated controls. Four-color flow cytometry was utilized to simultaneously identify three major porcine T-cell surface markers (CD4, CD8, and gammadelta TCR) and detect activation marker CD25 (alpha chain of IL-2 receptor) or intracellular IFNgamma. The MLV PRRSV vaccine alone successfully primed CD4(-)CD8(+)gammadelta- T-cells as demonstrated by a significant increase in %IFNgamma+ cells when live PRRSV was used as a recall antigen. Booster immunizations of mixed ORF5 peptides and co-administration of IL-12 with MLV PRRSV vaccine significantly enhanced IFNgamma expression by some T-cell subsets (CD4(-)CD8(+)gammadelta+ and CD4(-)CD8(-)gammadelta+ for mixed ORF5 peptides and CD4(+)CD8(+)gammadelta- and CD4(-)CD8(+)gammadelta+ for IL-12). All groups receiving MLV-vaccine with or without adjuvants had reduced lung lesions after challenge. The group immunized with only ORF5 peptide/CT did not have significant T-cell recall responses and was not protected from challenge. Expression of IFNgamma by several T-cell subsets correlated with reduced lung lesions and viremia, whereas expression of CD25 did not. Expression of surface CD25 did not correlate with IFNgamma production. PRRSV ELISA s/p ratio prior to challenge also correlated with reduced lung lesions and viremia. In conclusion, booster immunizations of the mixed ORF5 peptides and co-administration of IL-12 effectively enhanced the CMI response to MLV vaccine. However, neither adjuvant significantly contributed to reducing clinical effects when compared to MLV alone.

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