Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

Meulen, Jan ter; Bakker, Alexander B. H.; Brink, Edward N. van den; Weverling, Gerrit Jan; Martina, Byron; Haagmans, Bart L.; Kuiken, Thijs; Kruif, John de; Preiser, Wolfgang; Spaan, Willy J. M.; Gelderblom, Hans R.; Goudsmit, Jaap; Osterhaus, Albert D. M. E.

doi:10.1016/s0140-6736(04)16506-9

Cited by 253 publications

(240 citation statements)

References 5 publications

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“…The WKV+alum vaccine induced 15-fold higher serum neutralizing antibody titres than the other vaccines, but this vaccine did not provide universally better protection. While human antibodies to S protein have shown some protective effect against SARS in ferrets (ter Meulen et al, 2004), our results show that high systemic neutralizing (Table 3). Lung samples were fixed for histology and stained with haematoxylin and eosin or PAS.…”

Section: Discussionmentioning

confidence: 55%

“…Our ferret SARS-CoV challenge resulted in ferrets with clinical signs of infection (elevated temperature, nasal discharge and sneezing), in contrast to other reports using the same virus titre (Czub et al, 2005;ter Meulen et al, 2004;Weingartl et al, 2004). Our lab passed the Tor2 virus only once (a total of three passages) prior to challenge to avoid the accumulation of interfering particles or mutations due to tissue culture adaptation.…”

Section: Discussionmentioning

confidence: 97%

“…One limitation of mouse models is that they do not reproduce the clinical signs and severe disease of SARS in humans (Glass et al, 2004;Subbarao et al, 2004) unless aged mice are used (Rockx et al, 2007). Ferrets have been used widely for the study of influenza and are susceptible to SARS-CoV infection, exhibiting lung pathology and virus shedding (Martina et al, 2003;ter Meulen et al, 2004). One ferret study indicated that, upon intranasal (i.n.)…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

See

Petric

Lawrence

et al. 2008

Journal of General Virology

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Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage. INTRODUCTIONSevere acute respiratory syndrome (SARS) caused 8098 reported cases and 774 deaths in 26 countries (WHO, 2004a) in a single autumn-to-spring period from 2002 to 2003, and had significant effects on the global economy. Serological evidence suggests zoonotic transmission of SARS coronavirus (CoV) into the human population for several years before this outbreak (Zheng et al., 2004); transmission to humans has continued, resulting in at least four independent non-laboratory associated cases in (Che et al., 2006Fleck, 2004; Guan et al., 2005; WHO, 2004b). The aetiological agent of SARS has been identified as a novel human CoV by sequencing of its genome (Marra et al., 2003;Rota et al., 2003) and by experimental infection of macaques to fulfil Koch's postulates (Fouchier et al., 2003). It is of particular concern as a zoonosis because it can replicate in a large number of animals including cats, pigs, ferrets, foxes, monkeys and rats (Chen et al., 2005; et al., 1996;Olsen, 1993). Although antibodies to CoV N proteins have no virus-neutralizing activity, there is evidence that the protein may provide protection in vivo by induction of cell-mediated immunity, although it has also been suggested to induce eosinophilic infiltrates resulting in immunopathology (Deming et al., 2006;Enjuanes et al., 1995; Stohlman et al., 1995;Wesseling et al., 1993). N protein has been shown to generate CoV-specific CD8 + T cells (Boots et al., 1991;Seo et al., 1997; Stohlman et al., 1993 Stohlman et al., , 1995; it also provides protection in animals in response to infection by animal CoV (Collisson et al., 2000;Seo et al., 1997). In addition, vaccination with SARS N protein decre...

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

See

Petric

Lawrence

et al. 2008

Journal of General Virology

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“…The humanized mAb palivizumab that is used clinically for prophylaxis against respiratory syncytial virus infection is given at a dose of 15 mg/kg (41), which translates into a dose of ϳ375-450 g of mAb to a 25-30 g mouse. Similarly, a fully human Ab to the severe acute respiratory distress syndrome coronavirus was used at a dose of 10 mg/kg to protect ferrets against infection (42). Thus, our use of 50 -150 g delivered topically to the lung of a 30 g mouse is within the range of mAb doses used in either human clinical medicine or to evaluate human mAbs in animal models of infection.…”

Section: Discussionmentioning

confidence: 99%

Human Monoclonal Antibodies toPseudomonas aeruginosaAlginate That Protect against Infection by Both Mucoid and Nonmucoid Strains

Pier

Boyer

Preston

et al. 2004

The Journal of Immunology

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Two fully human mAbs specific for epitopes dependent on intact carboxylate groups on the C6 carbon of the mannuronic acid components of Pseudomonas aeruginosa alginate were found to promote phagocytic killing of both mucoid and nonmucoid strains as well as protection against both types of strains in a mouse model of acute pneumonia. The specificity of the mAbs for alginate was determined by ELISA and killing assays. Some strains of P. aeruginosa did not make detectable alginate in vitro, but in vivo protection against lethal pneumonia was obtained and shown to be due to rapid induction of expression of alginate in the murine lung. No protection against strains genetically unable to make alginate was achieved. These mAbs have potential to be passive therapeutic reagents for all strains of P. aeruginosa and the results document that alginate is a target for the proper type of protective Ab even when expressed at low levels on phenotypically nonmucoid strains.

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“…E, Equal amounts of the gradient fractions (nos. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] were examined by Western blot analyses. m8, m8-infected RK13 cell lysate; ppt, m8rVV-NMES-infected RK13cell lysate; PC, RK13 cell lysates infected with mOrVV-NHis, mOrVV-MHis, mOrVV-EHis, or mOrVV-SHis.…”

Section: Generation Of Recombinant Vv That Expresses the Structural Pmentioning

confidence: 99%

Prior Immunization with Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus (SARS-CoV) Nucleocapsid Protein Causes Severe Pneumonia in Mice Infected with SARS-CoV

Yasui¹,

Kai

Kitabatake³

et al. 2008

The Journal of Immunology

246

234

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The details of the mechanism by which severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia are unclear. We investigated the immune responses and pathologies of SARS-CoV-infected BALB/c mice that were immunized intradermally with recombinant vaccinia virus (VV) that expressed either the SARS-CoV spike (S) protein (LC16m8rVV-S) or simultaneously all the structural proteins, including the nucleocapsid (N), membrane (M), envelope (E), and S proteins (LC16m8rVV-NMES) 7–8 wk before intranasal SARS-CoV infection. The LC16m8rVV-NMES-immunized group exhibited as severe pneumonia as the control groups, although LC16m8rVV-NMES significantly decreased the pulmonary SARS-CoV titer to the same extent as LC16m8rVV-S. To identify the cause of the exacerbated pneumonia, BALB/c mice were immunized with recombinant VV that expressed the individual structural proteins of SARS-CoV (LC16mOrVV-N, -M, -E, -S) with or without LC16mOrVV-S (i.e., LC16mOrVV-N, LC16mOrVV-M, LC16mOrVV-E, or LC16mOrVV-S alone or LC16mOrVV-N + LC16mOrVV-S, LC16mOrVV-M + LC16mOrVV-S, or LC16mOrVV-E + LC16mOrVV-S), and infected with SARS-CoV more than 4 wk later. Both LC16mOrVV-N-immunized mice and LC16mOrVV-N + LC16mOrVV-S-immunized mice exhibited severe pneumonia. Furthermore, LC16mOrVV-N-immunized mice upon infection exhibited significant up-regulation of both Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-5) cytokines and down-regulation of anti-inflammatory cytokines (IL-10, TGF-β), resulting in robust infiltration of neutrophils, eosinophils, and lymphocytes into the lung, as well as thickening of the alveolar epithelium. These results suggest that an excessive host immune response against the nucleocapsid protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.

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Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

Cited by 253 publications

References 5 publications

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

Human Monoclonal Antibodies toPseudomonas aeruginosaAlginate That Protect against Infection by Both Mucoid and Nonmucoid Strains

Prior Immunization with Severe Acute Respiratory Syndrome (SARS)-Associated Coronavirus (SARS-CoV) Nucleocapsid Protein Causes Severe Pneumonia in Mice Infected with SARS-CoV

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