Protective Effect of the F(ab′)2 Fragments of Monoclonal Antibodies to Mouse Hepatitis Virus

Nakanaga, Kazue; Yamanouchi, Kazuya; Fujiwara, Kôsaku

doi:10.1007/978-1-4684-1280-2_45

Cited by 12 publications

(19 citation statements)

References 20 publications

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“…Whereas antibodies to N reportedly have no neutralizing activity in vitro Talbot et al, 1984;Nakanaga et al, 1986;Gilmore et al, 1987) a MAb to the protein prevented the c.p.e, of MHV in L cells (Lecomte et al, 1987). This antibody as well as another, non-neutralizing MAb (Nakanaga et al, 1986) protected mice from acute disease, in contrast to the lack of passive in vivo protection reported with several other anti-N antibodies (Hasony & MacNaughton, 1981 ;Buchmeier et al, 1984;Talbot et al, 1984). The mechanism by which the N protein in our studies provided such a strong protection is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies directed against the N protein do not neutralize virus in vitro but in some cases passive transfer of monoclonal antibodies (MAbs) specific to the N protein of MHV-2 (Nakanaga et al, 1986) and MHV-3 (Lecomte et al, 1987) protects mice from a lethal MHV infection. Furthermore, some MAbs directed against the M protein, in one case with virus-neutralizing activity in vitro, were shown to protect mice against a lethal MHV-4-induced hepatitis (Fleming et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

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Mouse hepatitis virus spike and nucleocapsid proteins expressed by adenovirus vectors protect mice against a lethal infection

Wesseling

Godeke

Schijns

et al. 1993

Journal of General Virology

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Infection with the mouse hepatitis coronavirus (MHV) provides an excellent model for the study of viral diseases of the central nervous system and the gastrointestinal tract. With the ultimate aim of studying mucosal immunity to MHV we have cloned the genes encoding the structural proteins of MHV strain A59 (MHV-A59) into the E3 region of a human adenovirus type 5 vector. Infection of HeLa cells with the resulting recombinant adenoviruses AdMHVS, AdMHVN and AdMHVM revealed the correct expression of the spike (S), nucleocapsid (N) and membrane (M) proteins, respectively. Intraperitoneal inoculation of BALB/c mice with the recombinant viruses elicited serum antibodies which specifically recognized the respective MHV proteins in an immunoprecipitation assay. Only antibodies to the S protein neutralized MHV-A59 in vitro but titres were low. When analysed by ELISA or by immunofluorescence only the antibody response to the N protein was significant; weak responses or no detectable response at all were found for S and M, respectively. Upon intracerebral challenge with a lethal dose of MHV-A59 we found that a significant fraction of animals vaccinated with adenovirus vectors expressing either the S protein or N protein were protected. This protective effect was significantly stronger when the animals were given a booster immunization with the same vector prior to challenge. No protection was induced by AdMHVM. Interestingly, enhanced protection resulted when AdMHVS and AdMHVN were applied in combination as compared to survival after single immunizations. The results indicate that both the N and S proteins generate a protective immune response and suggest that this response is enhanced by combined expression of the two proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mouse hepatitis virus spike and nucleocapsid proteins expressed by adenovirus vectors protect mice against a lethal infection

Wesseling

Godeke

Schijns

et al. 1993

Journal of General Virology

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“…Serum was collected from individuals who had experienced multiple infections in the past with more than one serotype of DENV as judged by clinical history and plaque reduction neutralization test (PRNT) titer analysis. The sera had the following reciprocal 50% PRNT titer (PRNT 50 ) values against DENV-1, DENV-2, DENV-3, and DENV-4: DENV-1 (640, 611, 213, and 319); DENV-2 (371, 320, 288, and Ͼ1,280); DENV-3 (Ͼ1,280, 300, 99, and 266); DENV-4 (Ͼ1,280, Ͼ1,280, Ͼ1,280, and 285); DENV-5 (589, Ͼ1,280, 717, and 82); DENV-6 (Ͼ1,280, Ͼ1,280, Ͼ1,280, and 187).…”

Section: Methodsmentioning

confidence: 99%

Poorly Neutralizing Cross-Reactive Antibodies against the Fusion Loop of West Nile Virus Envelope Protein ProtectIn Vivovia Fcγ Receptor and Complement-Dependent Effector Mechanisms

Vogt

Dowd

Engle

et al. 2011

J Virol

118

104

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The human antibody response to flavivirus infection is dominantly directed against a cross-reactive epitope on the fusion loop of domain II (DII-FL) of the envelope (E) protein. Although antibodies against this epitope fail to recognize fully mature West Nile virus (WNV) virions and accordingly neutralize infection poorly in vitro,their functional properties in vivo remain less well understood. Here, we show that while passive transfer of poorly neutralizing monoclonal antibodies (MAb) and polyclonal antibodies against the DII-FL epitope protect against lethal WNV infection in wild-type mice, they fail to protect mice lacking activating Fc␥ receptors (Fc␥R) and the complement opsonin C1q. Consistent with this, an aglycosyl chimeric mouse-human DII-FL MAb (E28) variant that lacks the ability to engage Fc␥R and C1q also did not protect against WNV infection in wild-type mice. Using a series of immunodeficient mice and antibody depletions of individual immune cell populations, we demonstrate that the nonneutralizing DII-FL MAb E28 does not require T, B, or NK cells, inflammatory monocytes, or neutrophils for protection. Rather, E28 treatment decreased viral load in the serum early in the course of infection, which resulted in blunted dissemination to the brain, an effect that required phagocytic cells, C1q, and Fc␥RIII (CD16). Overall, these studies enhance our understanding of the functional significance of immunodominant, poorly neutralizing antibodies in the polyclonal human antiflavivirus response and highlight the limitations of current in vitro surrogate markers of protection, such as cell-based neutralization assays, which cannot account for the beneficial effects conferred by these antibodies. West Nile virus (WNV) is a zoonotic mosquito-transmittedFlavivirus that can infect and cause disease in humans and many other vertebrate animals. The Flavivirus genus also contains other human pathogens of global relevance, including dengue virus (DENV), yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus. Most human WNV infections are asymptomatic, but about 20% of infected individuals experience a mild fever, and less than 1% develop severe neuroinvasive disease (67). Risk factors for symptomatic disease include an age of greater than 55 years, a compromised immune status, genetic variation in the OAS1 gene, and a CC5⌬32 genotype (17,26,40,41). Although WNV first appeared in the Western Hemisphere in 1999 in New York and spread rapidly through North America, surprisingly few human clinical infections have been reported in Central and South America, despite the migration of avian hosts and appropriate vectors for transmission (35,56).WNV infection requires attachment to cell surface receptors, which remain poorly defined, endocytosis, and acid-catalyzed fusion of the virus within the late endosome. After translation of input-strand RNA and viral replication, progeny virion assembly occurs within the endoplasmic reticulum (ER), with the capsid protein and genomic RNA associating with pre...

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“…The S protein is known to be a major target of the humoral and cellular immune response in CoV infection (8,63,70), and a protective effect of S-specific neutralizing antibodies has been documented (5,44). For that reason, we asked if sera from SARS patients recognize SARS-CoV S protein and neutralize infection by SARS-CoV S-bearing pseudotypes.…”

Section: An Antiserum Raised Against Purified Sars-cov Neutralizes Inmentioning

confidence: 99%

S Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Mediates Entry into Hepatoma Cell Lines and Is Targeted by Neutralizing Antibodies in Infected Patients

Hofmann

Hattermann

Marzi

et al. 2004

J Virol

184

204

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The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia with a fatal outcome in approximately 10% of patients. SARS-CoV is not closely related to other coronaviruses but shares a similar genome organization. Entry of coronaviruses into target cells is mediated by the viral S protein. We functionally analyzed SARS-CoV S using pseudotyped lentiviral particles (pseudotypes). The SARSCoV S protein was found to be expressed at the cell surface upon transient transfection. Coexpression of SARS-CoV S with human immunodeficiency virus-based reporter constructs yielded viruses that were infectious for a range of cell lines. Most notably, viral pseudotypes harboring SARS-CoV S infected hepatoma cell lines but not T-and B-cell lines. Infection of the hepatoma cell line Huh-7 was also observed with replicationcompetent SARS-CoV, indicating that hepatocytes might be targeted by SARS-CoV in vivo. Inhibition of vacuolar acidification impaired infection by SARS-CoV S-bearing pseudotypes, indicating that S-mediated entry requires low pH. Finally, infection by SARS-CoV S pseudotypes but not by vesicular stomatitis virus G pseudotypes was efficiently inhibited by a rabbit serum raised against SARS-CoV particles and by sera fromSARS patients, demonstrating that SARS-CoV S is a target for neutralizing antibodies and that such antibodies are generated in SARS-CoV-infected patients. Our results show that viral pseudotyping can be employed for the analysis of SARS-CoV S function. Moreover, we provide evidence that SARS-CoV infection might not be limited to lung tissue and can be inhibited by the humoral immune response in infected patients.

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Protective Effect of the F(ab′)2 Fragments of Monoclonal Antibodies to Mouse Hepatitis Virus

Cited by 12 publications

References 20 publications

Mouse hepatitis virus spike and nucleocapsid proteins expressed by adenovirus vectors protect mice against a lethal infection

Mouse hepatitis virus spike and nucleocapsid proteins expressed by adenovirus vectors protect mice against a lethal infection

Poorly Neutralizing Cross-Reactive Antibodies against the Fusion Loop of West Nile Virus Envelope Protein ProtectIn Vivovia Fcγ Receptor and Complement-Dependent Effector Mechanisms

S Protein of Severe Acute Respiratory Syndrome-Associated Coronavirus Mediates Entry into Hepatoma Cell Lines and Is Targeted by Neutralizing Antibodies in Infected Patients

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