Role of neutralizing antibodies in PRRSV protective immunity

Lopez, Osvaldo J.; Osorio, Fernando A.

doi:10.1016/j.vetimm.2004.09.005

Cited by 283 publications

(240 citation statements)

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“…Failure of PRRSV-infected piglets to develop a normal diversified repertoire with a neutral HCDR3 hydropathicity profile may explain why VN Ab responses are delayed (29), and Ͻ1% of the IgG is virus specific in PRRSV-infected isolator piglets (12). This may also explain why PRRSV establishes a persistent infection (40). Because the hypergammaglobulinemia we reported for PRRS elevates serum IgG, IgM, and IgA in proportion to the levels in fetal serum (60) and Ig aggregates of all three isotypes are deposited (12), we had no reason to suspect that B cell expansion is biased to IgG-secreting cells.…”

Section: Discussionmentioning

confidence: 99%

“…Despite a delay in virus-specific T cell responses, Ab responses to PRRSV of all major isotypes occur 6 -14 dpi in blood or BAL (34 -36). IL-10 is up-regulated (37-39), but the appearance of virus-neutralizing (VN) Abs and CD4 ϩ antiviral responses is delayed until 28 dpi (40). When present, VN is often mediated by Abs to open reading frame (ORF)5 glycoprotein (41,42) and to a lesser extent epitopes on the M protein (membrane protein, ORF6; 43), even through robust responses to this highly immunogenic nucleocapsid protein (N protein, ORF7) are seen (44,45).…”

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confidence: 99%

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Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

Butler

Lemke

Weber

et al. 2007

The Journal of Immunology

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Porcine respiratory and reproductive syndrome virus (PRRSV) causes an extraordinary increase in the proportion of B cells resulting in lymphoid hyperplasia, hypergammaglobulinemia, and autoimmunity in neonatal piglets. Spectratypic analysis of B cells from neonatal isolator piglets show a non-Gaussian pattern with preferential expansion of clones bearing certain H chain third complementary region (HCDR3) lengths. However, only in PRRSV-infected isolator piglets was nearly the identical spectratype observed for all lymphoid tissues. This result suggests dissemination of the same dominant B cell clones throughout the body. B cell expansion in PRRS was not associated with preferential VH gene usage or repertoire diversification and these cells appeared to bear a naive phenotype. The B cell population observed during infection comprised those with hydrophobic HCDR3s, especially sequences encoded by reading frame 3 of DHA that generates the AMVLV motif. Thus, the hydropathicity profile of B cells after infection was skewed to favor those with hydrophobic binding sites, whereas the normally dominant region of the hydropathicity profile containing neutral HCDR3s was absent. We believe that the hypergammaglobulinemia results from the products of these cells. We speculate that PRRSV infection generates a product that engages the BCR of naive B cells, displaying the AMVLV and similar motifs in HCDR3 and resulting in their T-independent proliferation without repertoire diversification.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

Butler

Lemke

Weber

et al. 2007

The Journal of Immunology

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“…The VN antibodies response detected at 10 days post-challenge was the specific consequence of prior immunization with hAdV/synORF5 since normally, VN antibodies are detected after only 3 to 4 weeks in SPF pigs experimentally-or naturallyinfected with PRRSV [10,20]. The higher reactivity to GP5, as well as the higher VN activity of pigs sera that have been vaccinated either with hAdV/wtORF5 or hAdV/synORF5 is in agreement with previous findings indicating that GP5 is the primary structural glycoprotein of PRRSV involved in virus neutralization activity [6,7,25].…”

Section: Discussionmentioning

confidence: 99%

“…These findings suggest also that the amounts of GP5 synthesized in the infected cells, as well as conformation of the protein which may be influenced by the type of oligosaccharide side chains present on the molecule, are apparently crucial to trigger an effective humoral immune response to PRRSV. Since a correlation may exist amongst protection, clinical course of the disease, and seroneutralizing antibody titers [9,10], the present study was designed to increase the efficacy of genetic immunization against antigenic determinants of GP5.…”

Section: Introductionmentioning

confidence: 99%

Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP5 glycoprotein and improves immune response in challenged pigs

Kheyar

Jabrane

Zhu

et al. 2005

Vaccine

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Pigs exposed to GP5 protein of PRRSV by means of DNA immunization develop specific neutralizing and protecting antibodies. Herein, we report on the consequences of codon bias, and on the favorable outcome of the systematic replacement of native codons of PRRSV ORF5 gene with codons chosen to reflect more closely the codon preference of highly expressed mammalian genes. Therefore, a synthetic PRRSV ORF5 gene (synORF5) was constructed in which 134 nucleotide substitutions were made in comparison to wild-type gene (wtORF5), such that 59% (119) of wild-type codons were replaced with known preferable codons in mammalian cells. In vitro expression in mammalian cells of synORF5 was considerably increased comparatively to wtORF5, following infection with tetracycline inducible replication-defective human adenoviral vectors (hAdVs). After challenge inoculation, SPF pigs vaccinated twice with recombinant hAdV/synORF5 developed earlier and higher antibody titers, including virus neutralizing antibodies to GP5 than pigs vaccinated with hAdV/wtORF5. Data obtained from animal inoculation studies suggest direct correlation between expression levels of immunogenic structural viral proteins and immune response

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“…PRRSV targets primarily a subpopulation of macrophages in the lung and other tissues that have reached a specific stage of differentiation that renders them permissive to the virus (Duan et al, 1997;Gaudrealt et al, 2009). PRRSV infection is characterised by an atypical pathogenesis consisting of a prolonged acute phase lasting for 1 month or longer, with peak virus levels in the blood and lung between 7 to 14 days post infection and followed by a persistent infection in the lung and lymphoid tissues that clears for most animals within 150 days post infection (Allende et al, 2000), but can last in some (especially younger) pigs for several months or years (Lopez and Osorio, 2004;Figure 3a).…”

Section: Prrsv (Virus) Infection (See Example 1)mentioning

confidence: 99%

The role of mathematical models of host–pathogen interactions for livestock health and production – a review

Doeschl‐Wilson

2011

Animal

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Compared with the application of mathematical models to study human diseases, models that describe animal responses to pathogen challenges are relatively rare. The aim of this review is to explain and show the role of mathematical host-pathogen interaction models in providing underpinning knowledge for improving animal health and sustaining livestock production. Existing host-pathogen interaction models can be assigned to one of three categories: (i) models of the infection and immune system dynamics, (ii) models that describe the impact of pathogen challenge on health, survival and production and (iii) models that consider the co-evolution of host and pathogen. State-of-the-art approaches are presented and discussed for models belonging to the first two categories only, as they concentrate on the host-pathogen dynamics within individuals. Models of the third category fall more into the class of epidemiological models, which deserve a review by themselves. An extensive review of published models reveals a rich spectrum of methodologies and approaches adopted in different modelling studies, and a strong discrepancy between models concerning diseases in animals and models aimed at tackling diseases in humans (most of which belong to the first category), with the latter being generally more sophisticated. The importance of accounting for the impact of infection not only on health but also on production poses a considerable challenge to the study of host-pathogen interactions in livestock. This has led to relatively simplistic representations of host-pathogen interaction in existing models for livestock diseases. Although these have proven appropriate for investigating hypotheses concerning the relationships between health and production traits, they do not provide predictions of an animal's response to pathogen challenge of sufficient accuracy that would be required for the design of appropriate disease control strategies. A synthesis between the modelling methodologies adopted in categories 1 and 2 would therefore be desirable. The progress achieved in mathematical modelling to study immunological processes relevant to human diseases, together with the current advances in the generation and analysis of biological data related to animal diseases, offers a great opportunity to develop a new generation of host-pathogen interaction models that take on a fundamental role in the study and control of disease in livestock.

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Role of neutralizing antibodies in PRRSV protective immunity

Cited by 283 publications

References 56 publications

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP5 glycoprotein and improves immune response in challenged pigs

The role of mathematical models of host–pathogen interactions for livestock health and production – a review

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