Prospects for a virus non-structural protein as a subunit vaccine

Gibson, C.A.; Schlesinger, Jacob J.; Barrett, Alan D.T.

doi:10.1016/0264-410x(88)90004-7

Cited by 34 publications

(19 citation statements)

References 23 publications

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“…Schlesinger et al (1985Schlesinger et al ( , 1986Schlesinger et al ( , 1990 proposed that immune recognition of NS1 and consequent cytolysis afford an alternative to virion neutralization by antibodies in protection against flavivirus infection. These data support the idea that the nonstructural NS1 protein could be used as a component of a subunit vaccine against flavivirus infection (Gibson et al, 1988).…”

supporting

confidence: 75%

Recombinant baculoviruses expressing yellow fever virus E and NS1 proteins elicit protective immunity in mice

Desprès

Diétrich

Girard

et al. 1991

Journal of General Virology

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Recently, we showed that yellow fever virus (YFV) E and NS1 proteins in Spodoptera frugiperda cells infected with a recombinant baculovirus are similar, if not identical to those produced during YFV infection. To study the role of E and NS1 in the induction of protective immunity against fatal YFV challenge, these viral antigens were expressed either alone or in tandem via recombinant baculoviruses Ac-E.NS1, Ac-E1 and Ac-NS1. Swiss mice were immunized with lysates of insect cells infected with the recombinant baculoviruses. Solid protection against lethal YFV encephalitis was achieved after immunization with cell lysates containing the E protein with or without the NS1 protein. Mice inoculated with recombinant protein NS1 alone were not significantly protected but showed an increased survival time. Recombinant E protein expressed alone or in tandem with NS 1 elicited a low but significant level of neutralizing antibodies. Although protein NS1 synthesized by recombinant baculovirus expressing E plus NS 1 was more immunogenic than that expressed alone, neither strategy induced NSl-specific antibodies with complementmediated cytolytic activity.

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supporting

confidence: 75%

Recombinant baculoviruses expressing yellow fever virus E and NS1 proteins elicit protective immunity in mice

Desprès

Diétrich

Girard

et al. 1991

Journal of General Virology

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“…Future studies using error-prone PCR mutagenesis and yeast surface display are planned to identify the amino acid contact residues for many of the individual MAbs against WNV NS1. Because some antibodies against flavivirus NS1 protect against lethal infection in vivo, immunization with purified NS1 has been proposed as an alternative vaccination strategy against flaviviruses (26,33,34,44,62,63,71,75). Indeed, immunization with a single NS1 peptide (amino acids 37 to 55) of TBE elicited antibodies that protected mice against lethal challenge (65).…”

Section: Discussionmentioning

confidence: 99%

Antibodies against West Nile Virus Nonstructural Protein NS1 Prevent Lethal Infection through Fc γ Receptor-Dependent and -Independent Mechanisms

Chung

Nybakken

Thompson

et al. 2006

J Virol

226

239

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The flavivirus nonstructural protein NS1 is a highly conserved secreted glycoprotein that does not package with the virion. Immunization with NS1 elicits a protective immune response against yellow fever, dengue, and tick-borne encephalitis flaviviruses through poorly defined mechanisms. In this study, we purified a recombinant, secreted form of West Nile virus (WNV) NS1 glycoprotein from baculovirus-infected insect cells and generated 22 new NS1-specific monoclonal antibodies (MAbs). By performing competitive binding assays and expressing truncated NS1 proteins on the surface of yeast (Saccharomyces cerevisiae) and in bacteria, we mapped 21 of the newly generated MAbs to three NS1 fragments. Prophylaxis of C57BL/6 mice with any of four MAbs (10NS1, 14NS1, 16NS1, and 17NS1) strongly protected against lethal WNV infection (75 to 95% survival, respectively) compared to saline-treated controls (17% survival). In contrast, other anti-NS1 MAbs of the same isotype provided no significant protection. Notably, 14NS1 and 16NS1 also demonstrated marked efficacy as postexposure therapy, even when administered as a single dose 4 days after infection. Virologic analysis showed that 17NS1 protects at an early stage in infection through a C1q-independent and Fc ␥ receptor-dependent pathway. Interestingly, 14NS1, which maps to a distinct region on NS1, protected through a C1q-and Fc ␥ receptor-independent mechanism. Overall, our data suggest that distinct regions of NS1 can elicit protective humoral immunity against WNV through different mechanisms.West Nile virus (WNV) is a single-stranded, positive-senseenveloped RNA virus that is maintained in nature through a mosquito-bird-mosquito transmission cycle. It is endemic in parts of Africa, Europe, the Middle East, and Asia, and outbreaks now occur annually in North America. Humans, which are dead-end hosts, can develop a febrile illness that progresses to a meningitis or encephalitis syndrome (32). At present, treatment is supportive, and no vaccine exists for human use.A member of the Flaviviridae family, WNV is closely related to other major human pathogens such as yellow fever (YF), dengue (DEN), tick-borne encephalitis (TBE), Japanese encephalitis (JEV), and Murray Valley encephalitis (MVE) viruses. The 10.7-kilobase genome is translated as a single polyprotein, which is then cleaved into three structural proteins (C, prM/M, and E) and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) by both virus-and host-encoded proteases (5). The NS proteins include an RNA-dependent RNA polymerase (NS5), a helicase/protease (NS3), and other proteins that form part of the viral replication complex (36, 37).NS1 is a highly conserved 48-kDa glycoprotein with 12 invariant cysteine residues. Although the disulfide linkage arrangement of MVE and DEN NS1 has been described (4, 66), structural analysis is currently lacking. NS1 is inserted into the lumen of the endoplasmic reticulum via a signal peptide that is cleaved cotranslationally by a cellular signalase to gene...

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“…The fact that non-structural proteins can be involved in the induction of cell-mediated responses and in resistance to infection (Gibson et al, 1988) led us to examine in vitro T cell proliferative responses to NS3, one of the major non-structural polypeptides of BVDV. In this study, recombinant Osloss strain NS3 protein was recognized by lymphocytes from five of six experimental subgroups while non-cytopathic or cytopathic virus preparations were recognized in all calves infected.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the immune response of cattle against non-cytopathic and cytopathic biotypes of bovine viral diarrhoea virus.

Lambot

Douart

Joris

et al. 1997

Journal of General Virology

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Cross-infection studies of normal calves infected with homologous pairs of non-cytopathic and cytopathic bovine viral diarrhoea virus (BVDV) showed significant differences in both humoral and cellmediated immune responses against either biotype over a period of 5 months. Serological assays after primary intranasal inoculation showed striking significant (P 0n05) differences between biotypes. Neutralizing titres were detected earlier and were much higher with the non-cytopathic strain than with the homologous cytopathic strain. Significant biotype-specific differences were also observed in the lymphocyte proliferative responses of cattle following in vitro stimulation by non-cytopathic/ cytopathic BVDV and the non-structural p80 protein (NS3). The secondary immune response seems to be largely influenced by the biotype used for the primary inoculation and only to a lesser extent by the biotype inoculated for the second time after an

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Prospects for a virus non-structural protein as a subunit vaccine

Cited by 34 publications

References 23 publications

Recombinant baculoviruses expressing yellow fever virus E and NS1 proteins elicit protective immunity in mice

Recombinant baculoviruses expressing yellow fever virus E and NS1 proteins elicit protective immunity in mice

Antibodies against West Nile Virus Nonstructural Protein NS1 Prevent Lethal Infection through Fc γ Receptor-Dependent and -Independent Mechanisms

Characterization of the immune response of cattle against non-cytopathic and cytopathic biotypes of bovine viral diarrhoea virus.

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