Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology.
[en] Respiratory syncytial virus (RSV) is a major cause of respiratory disease in both cattle and young children. Despite the development of vaccines against bovine (B)RSV, incomplete protection and exacerbation of subsequent RSV disease have occurred. In order to circumvent these problems, calves were vaccinated with the nucleocapsid protein, known to be a major target of CD8(+) T cells in cattle. This was performed according to a DNA prime-protein boost strategy. The results showed that DNA vaccination primed a specific T-cell-mediated response, as indicated by both a lymphoproliferative response and IFN-gamma production. These responses were enhanced after protein boost. After challenge, mock-vaccinated calves displayed gross pneumonic lesions and viral replication in the lungs. In contrast, calves vaccinated by successive administrations of plasmid DNA and protein exhibited protection against the development of pneumonic lesions and the viral replication in the BAL fluids and the lungs. The protection correlated to the cell-mediated immunity and not to the antibody response.
Disciplines :
Immunology & infectious disease Microbiology Veterinary medicine & animal health
Vaccination of calves using the BRSV nucleocapsid protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects the lungs against BRSV replication and pathology.
Brandenburg, A.H., Neijens, H.J., Osterhaus, A.D.M.E., Pathogenesis of RSV lower respiratory tract infection: implications for vaccine development (2001) Vaccine, 19, pp. 2769-2782
Larsen, L.E., Bovine respiratory syncytial virus (BRSV): a review (2000) Acta Vet Scand, 41, pp. 1-24
Van der Poel, W.H., Brand, A., Kramps, J.A., Van Oirschot, T.J., Respiratory syncytial virus infections in human beings and in cattle (1994) J Infect, 29, pp. 215-228
Belknap, E.B., Baker, J.C., Patterson, J.S., Walker, R.D., Haines, D.M., Clark, E.G., The role of passive immunity in bovine respiratory syncytial virus-infected calves (1991) J Infect Dis, 163, pp. 470-476
Kimman, T.G., Westenbrink, F., Schreuder, B.E.C., Straver, P.J., Local and systemic antibody response to bovine respiratory syncytial virus infection and reinfection in calves with and without maternal antibodies (1987) J Clin Microbiol, 25, pp. 1097-1106
Kimman, T.G., Zimmer, G.M., Westenbrink, F., Mars, J., van Leeuwen, E., Epidemiological study of bovine respiratory syncytial virus infections in calves: Influence of maternal antibodies on the outcome of disease (1988) Vet Rec, 123, pp. 104-109
Ellis, J.A., The immunology of the bovine respiratory disease complex (2001) Vet Clin North Am Food Anim Pract, 17, pp. 535-550
Peters, A.R., Thevasagayam, S.J., Wieseman, A., Salt, J.S., Duration of immunity of a quadrivalent vaccine against respiratory diseases caused by BHV-1, PIV3, BVDV, and BRSV in experimentally infected calves (2004) Prev Vet Med, 66, pp. 63-77
Patel, J.R., Didlick, S.A., Evaluation of efficacy of an inactivated vaccine against BRSV in calves with maternal antibodies (2004) Am J Vet Res, 65, pp. 417-421
Ellis, J., Gow, S., West, K., Waldner, C., Rhodes, C., Mutwiri, G., Response of calves to challenge exposure with virulent BRSV following intranasal administration of vaccines formulated for parenteral administration (2007) J Am Vet Med Assoc, 15, pp. 233-243
Kim, H.W., Canchola, J.G., Brandt, C.D., Pyles, G., Chanock, R.M., Jensen, K., Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine (1969) Am J Epidemiol, 89, pp. 422-434
Gershwin, L.J., Schelegle, E.S., Gunther, R.A., Anderson, M.L., Woolums, A.R., Larochelle, D.R., A bovine model of vaccine enhanced respiratory syncytial virus pathophysiology (1998) Vaccine, 16, pp. 1225-1236
Hussell, T., Baldwin, C.J., O'Garra, A., Openshaw, P.J., CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection (1997) Eur J Immunol, 27, pp. 3341-3349
Varga, S.M., Wang, X., Welsh, R.M., Braciale, T.J., Immunopathology in RSV infection is mediated by a discrete oligoclonal subset of antigen-specific CD4(+) T cells (2001) Immunity, 15, pp. 637-646
Connors, M., Giese, N.A., Kulkarni, A.B., Firestone, C.Y., Morse III, H.C., Murphy, B.R., Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10 (1994) J Virol, 68, pp. 5321-5325
Antonis, A.F.G., Schrijver, R.S., Daus, F., Steverink, P.J.G.M., Stockhofe, N., Hensen, E.J., Vaccine-induced immunopathology during bovine respiratory syncytial virus infection: exploring the parameters of pathogenesis (2003) J Virol, 77, pp. 12067-12073
Gershwin, L.J., Gunther, R.A., Anderson, M.L., Woolums, A.R., McArthur- Vaughan, K., Randel, K.E., Bovine respiratory syncytial virus-specific IgE is associated with interleukin-2 and -4, and interferon-gamma expression in pulmonary lymph of experimentally infected calves (2000) Am J Vet Res, 61, pp. 291-298
Kalina, W.V., Woolums, A.R., Berghaus, R.D., Gershwin, L.J., Formalin-inactivated bovine RSV vaccine enhances a Th2 mediated immune response in infected cattle (2004) Vaccine, 22, pp. 1465-1474
Schreiber, P., Matheise, J.P., Dessy, F., Heimann, M., Letesson, J.-J., Coppe, P., High mortality rate associated with bovine respiratory syncytial virus (BRSV) infection in Belgian white blue calves previously vaccinated with an inactivated BRSV vaccine (2000) J Vet Med B Infect Dis Vet Public Health, 47, pp. 535-550
Larsen, L.E., Tegtmeier, C., Pedersen, E., Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination (2001) Acta Vet Scand, 42, pp. 113-121
Taylor, G., Thomas, L.H., Furze, J.M., Cook, R.S., Wyld, S.G., Lerch, R., Recombinant vaccinia viruses expressing the F, G or N, but not the M2, protein of bovine respiratory syncytial virus (BRSV) induce resistance to BRSV challenge in the calf and protect against the development of pneumonic lesions (1997) J Gen Virol, 78, pp. 3195-3206
Thomas, L.H., Cook, R.S., Wyld, S.G., Furze, J.M., Taylor, G., Passive protection of gnotobiotic caves using monoclonal antibodies directed at different epitopes on the fusion protein of bovine respiratory syncytial virus (1998) J Infect Dis, 177, pp. 874-880
Taylor, G., Thomas, L.H., Wyld, S.G., Furze, J.M., Sopp, P., Howard, C.J., Role of T-lymphocyte subsets in recovery from respiratory syncytial virus infection in calves (1995) J Virol, 69, pp. 6658-6664
Braciale, T.J., Respiratory Syncytial virus and T cells Interplay between the virus and the host adaptive immune system (2005) Proc Am Thorac Soc, 2, pp. 141-146
Openshaw, P.J., Tregoning, J.S., Immune responses and disease enhancement during respiratory syncytial virus infection (2005) Clin Microbiol Rev, 18, pp. 541-555
Bangham, C.R., Openshaw, P.J., Ball, L.A., King, A.M., Wertz, G.W., Askonas, B.A., Human and murine cytotoxic T cells specific to respiratory syncytial virus recognize the viral nucleoprotein (N), but not the major glycoprotein (G), expressed by vaccinia virus recombinants (1986) J Immunol, 137, pp. 3973-3977
Connors, M., Kulkarni, A.B., Collins, P.L., Firestone, C.-Y., Holmes, K.L., Morse, H.C., Resistance to respiratory syncytial virus (RSV) challenge induced by infection with a vaccinia virus recombinant expressing the RSV M2 protein is mediated by CD8+ T cells, while that induced by Vac-F or Vac-G recombinants is mediated by antibodies (1992) J Virol, 66, pp. 1277-1281
Gaddum, R.M., Cook, R.S., Furze, J.M., Ellis, S.A., Taylor, G., Recognition of bovine respiratory syncytial virus proteins by bovine CD8+ T lymphocytes (2003) Immunology, 108, pp. 220-229
Antonis, A.F.G., Claassen, E.A.W., Hensen, E.J., de Groot, R.J., de Groot-Mijnes, J.D.F., Schrijver, R.S., Kinetics of antiviral CD8 T cell responses during primary and post-vaccination secondary bovine respiratory syncytial virus infection (2006) Vaccine, 24, pp. 1551-1561
Gaddum, R.M., Cook, R.S., Thomas, L.H., Taylor, G., Primary cytotoxic T-cell responses to bovine respiratory syncytial virus in calves (1996) Immunology, 88, pp. 421-427
McInnes, E., Sopp, P., Howard, C.J., Taylor, G., Phenotypic analysis of local cellular responses in calves infected with bovine respiratory syncytial virus (1999) Immunology, 96, pp. 396-403
Rutigliano, J.A., Johnson, T.R., Hollinger, T.N., Fischer, J.E., Aung, S., Graham, B.S., Treatment with anti-LFA-1 delays the CD8+ cytotoxic-T-lymphocyte response and viral clearance in mice with primary respiratory syncytial virus infection (2004) J Virol, 78, pp. 3014-3023
Srikiatkhachorn, A., Braciale, T.J., Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection (1997) J Exp Med, 186, pp. 421-432
Robinson, H.L., Pertmer, T.M., DNA vaccines for viral infections: basic studies and applications (2000) Adv Virus Res, 55, pp. 1-74
Bembridge, G.P., Rodriguez, N., Garcia-Beato, R., Nicolson, C., Melero, J.A., Taylor, G., DNA encoding the attachment (G) or fusion (F) protein of respiratory syncytial virus induces protection in the absence of pulmonary inflammation (2000) J Gen Virol, 81, pp. 2519-2523
Brady, R.P., Topliff, C.L., Kelling, C.L., In vitro expression of full-length and truncated bovine respiratory syncytial virus G proteins and their antibody responses in BALB/c mice (2004) Vaccine, 22, pp. 3762-3768
Babiuk, L.A., Pontarollo, R., Babiuk, S., Loehr, B., van Drunen Littel-van den Hurk, S., Induction of immune response by DNA vaccines in large animals (2003) Vaccine, 21, pp. 649-658
Toussaint, J.F., Letellier, C., Paquet, D., Dispas, M., Kerkhofs, P., Prime-boost strategies combining DNA and inactivated vaccines confer high immunity and protection in cattle against bovine herpesvirus-1 (2005) Vaccine, 23, pp. 5073-5081
Boxus, M., Tignon, M., Toussaint, J.-F., Roels, S., Benoit, M.A., Walravens, K., DNA immunization against fusion and nucleocapsid proteins protects calves against BRSV (2007) J Virol, 81, pp. 6879-6889
Martinez, X., Li, X., Kovarik, J., Klein, M., Lambert, P.-H., Siegrist, C.-A., Combining DNA and protein vaccination for early life immunization against RSV in mice (1999) Eur J Immunol, 29, pp. 3390-3400
Samal, S.K., Zamora, M., McPhillips, T.H., Mohanty, S.B., Molecular cloning and sequence analysis of Bovine Respiratory Syncytial Virus mRNA encoding the major nucleocapsid protein (1991) Virology, 180, pp. 453-456
Tjornehoj, K., Uttenthal, A., Viuff, B., Larsen, L.E., Rontved, C., Ronsholt, L., An experimental infection model for reproduction of calf pneumonia with bovine respiratory syncytial virus (BRSV) based on one combined exposure of calves (2003) Res Vet Sci, 74, pp. 55-65
Wellemans, G., Leunen, J., La Rhino-trachéite infectieuse des bovins et sa sérologie (1973) Ann Méd Vét, 117, p. 507518
Uttenthal, A., Larsen, L.E., Philipsen, J.S., Tjornehoj, K., Viuff, B., Nielsen, K.H., Antibidy dynamics in BRSV-infected Danish dairy herds as determined by isotype-specific immunoglobulins (2000) Vet Microbiol, 76, pp. 329-341
Boxus, M., Letellier, C., Kerkhofs, P., Real Time RT-PCR for the detection and quantitation of bovine respiratory syncytial virus (2005) J Virol Methods, 125, pp. 125-130
Gurunathan, S., Klinman, D.M., Seder, R.A., DNA vaccines: immunology, application, and optimization (2000) Annu Rev Immunol, 18, pp. 927-974
Van Drunen Little-van den Hurk, S., Braun, R.P., Lewis, P.J., Karvonen, B.C., Babiuk, L.A., Griebel, P.J., Immunization of neonates with DNA encoding a bovine herpesvirus glycoprotein is effective in the presence of maternal antibodies (1999) Viral Immunol, 12, pp. 67-77
Martinez, X., Brandt, C., Saddallah, F., Tougne, C., Barrios, C., Wild, F., DNA immunization circumvents deficient induction of TH1 and cytotoxic T cells lymphocyte responses in neonates and during early life (1997) PNAS, 94, pp. 8726-8731
Morein, B., Abusugra, I., Blomqvist, G., Immunity in neonates (2002) Vet Immunol Immunopathol, 87, pp. 207-213
Li, X., Sambhara, S., Li, C.X., Ewasyshyn, M., Parrington, M., Caterini, J., Protection against respiratory syncytial virus infection by DNA immunization (1998) J Exp Med, 188, pp. 681-688
Li, X., Sambhara, S., Li, C.X., Ettorre, L., Switzer, I., Cates, G., Plasmid DNA encoding the respiratory syncytial virus G protein is a promising vaccine candidate (2000) Virology, 269, pp. 54-65
Schrijver, R.S., Langedijk, J.P., Keil, G.M., Middel, W.G.J., Maris-Veldhuis, M., Van Oirschot, J.T., Immunization of cattle with a BHV1 vector vaccine or a DNA vaccine both coding for the G protein of BRSV (1997) Vaccine, 15, pp. 1908-1916
Schrijver, R.S., Langedijk, J.P., Keil, G.M., Middel, W.G.J., Maris-Veldhuis, M., Van Oirschot, J.T., Comparison of DNA application methods to reduce BRSV shedding in cattle (1998) Vaccine, 16, pp. 130-134
Taylor, G., Bruce, C., Barbet, A.F., Wyld, S.G., Thomas, L.H., DNA vaccination against respiratory syncytial virus in young calves (2005) Vaccine, 23, pp. 1242-1250
Vaughan, K., Rhodes, G.H., Gershwin, L.J., DNA immunization against respiratory syncytial virus (RSV) in infant rhesus monkeys (2005) Vaccine, 23, pp. 2928-2942
King, A.M.Q., Stott, E.J., Langer, S.J., Young, K.K.-Y., Ball, L.A., Wertz, G.W., Recombinant vaccinia virus carrying the N gene of Human respiratory syncytial virus: studies of gene expression in cell culture and immune response in mice (1987) J Virol, 61, pp. 2885-2890
Connors, M., Collins, P.L., Firestone, C.-Y., Murphy, B., Respiratory syncytial virus (RSV) F, G, M2, and N proteins each induce resistance to RSV challenge, but resistance induced by M2 and N proteins is relatively short-lived (1991) J Virol, 65, pp. 1634-1637
Grell, S.N., Riber, U., Tjornehoj, K., Larsen, L.E., Heegaard, P.M.H., Age-dependent differences in cytokine and antibody responses after experimental RSV infection in a bovine model (2005) Vaccine, 23, pp. 3412-3423
Viuff, B., Tjornehoj, K., Larsen, L.E., Rontved, C., Uttenthal, A., Ronsholt, L., Replication and clearance of respiratory syncytial virus apoptosis is an important pathway of virus clearance after experimental infection with BRSV (2002) Am J Pathology, 161, pp. 2195-2207
Estes, D.M., Brown, W.C., Type 1 and type 2 responses in regulation of Ig isotype expression in cattle (2002) Vet Immunol Immunopathol, 90, pp. 1-10
Cannon, M.J., Openshaw, P.J., Askonas, B.A., Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus (1988) J Exp Med, 168, pp. 1163-1168
Ostler, T., Davidson, W., Ehl, S., Virus clearance and immunopathology by CD8(+) T cells during infection with respiratory syncytial virus are mediated by IFN-gamma (2002) Eur J Immunol, 32, pp. 2117-2123
Aung, S., Tang, Y.W., Graham, B.S., Interleukin-4 diminishes CD8(+) respiratory syncytial virus-specific cytotoxic T lymphocyte activity in vivo (1999) J Virol, 73, pp. 8944-8949
Woolums, A.R., Singer, R.S., Boyle, G.A., Gershwin, L.J., Interferon gamma production during bovine respiratory syncytial virus (BRSV) infection is diminished in calves vaccinated with formalin-inactivated BRSV (1999) Vaccine, 17, pp. 1293-1297
Oumouna, M., Mapletoft, J.W., Karvonen, B.C., Babiuk, L.A., van Drunen Littel-van den Hurk, S., Formulation with CpG oligodeoxynucleotides prevents induction of pulmonary immunopathology following priming with formalin-inactivated or commercial killed bovine respiratory syncytial virus vaccine (2005) J Virol, 79, pp. 2024-2032
Mapletoft, J.W., Oumouna, M., Townsend, H.G., Gomis, S., Babiuk, L.A., van Drunen Littel-van den Hurk, S., Formulation with CpG oligodeoxynucleotides increases cellular immunity and protection induced by vaccination of calves with formalin-inactivated bovine respiratory syncytial virus (2006) Virology, 353, pp. 316-323
West, K., Petrie, L., Konoby, C., Haines, D.M., Cortese, V., Ellis, J.A., The efficacy of modified-live bovine respiratory syncytial virus vaccines in experimentally infected calves (2000) Vaccine, 18, pp. 907-919
Sharma, A.K., Woldehiwet, Z., Walravens, K., Letesson, J., Immune response of lambs to the fusion glycoprotein of BRSV expressed on insect cells infected with a recombinant baculovirus (1996) Vaccine, 14, pp. 773-779
Abe, T., Takahashi, H., Hamazaki, H., Miyano-kurosaki, N., Matsuura, Y., Takaku, H., Baculovirus induces an innate immune response and confers protection from lethal Influenza virus infection in mice (2003) J Immunol, 171, pp. 1133-1139
Liang, R., van den Hurk, J.V., Babiuk, L.A., van Drunen Littel-van den Hurk, S., Priming with DNA encoding E2 and boosting with E2 protein formulated with CpG oligodeoxynucleotides induces strong immune responses and protection from Bovine viral diarrhea virus in cattle (2006) J Gen Virol, 87, pp. 2971-2982
Estcourt, M.J., Ramsay, A.J., Brooks, A., Thomson, S.A., Medveckzy, C.J., Ramshaw, I.A., Prime-boost immunization generates a high frequency, high-avidity CD8(+) cytotoxic T lymphocyte population (2002) Int Immunol, 14, pp. 31-37
Loehr, B.I., Pontarollo, R., Rankin, R., Latimer, L., Willson, P., Babiuk, L.A., Priming by DNA immunization augments T-cell responses induced by modified live bovine herpesvirus vaccine (2001) J Gen Virol, 82, pp. 3035-3043
Kong, W.-p., Xu, l., Stadler, K., Ulmer, J.B., Abrignani, S., Rappuoli, R., Modulation of the immune response to the severe acute respiratory syndrome spike glycoprotein by gene-based and inactivated virus immunization (2005) J Virol, 79, pp. 13915-13923
Cristillo, A.D., Wang, S., Caskey, M.S., Unangst, T., Hocker, L., He, L., Preclinical evaluation of cellular immune responses elicited by a polyvalent DNA prime/protein boost HIV-1 vaccine (2006) Virology, 346, pp. 151-168