Immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the NS1 non-structural protein.

Timofeev, A.; Ozherelkov, S V; Пронин, А. В.; Deeva, A V; Karganova, Galina G.; Elbert, L. B.; Stephenson, J R

doi:10.1099/0022-1317-79-4-689

Cited by 37 publications

(26 citation statements)

References 38 publications

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“…Another factor may have been the generation of antibodies to NS1 by live viral immunisation but not by Biken vaccination (as Biken is purified inactivated virions with little or no NS1 present). Antibody to NS1 has been shown to be protective against experimental infections with flaviviruses [Schlesinger at al., 1985;Gould et al, 1986;Hall et al, 1996;Timofeev et al, 1998] and to play a role in protection against experimental infection with Tick borne 7.1 ± 1.0 (P ‫ס‬ 0.001) 100 Arc/S 1/10 Biken 1:10 7.5 ± 0.9 (P ‫ס‬ 0.06) 100 8.8 ± 2.4 (P ‫ס‬ 0.15) 90 Repeat experiment 7.1 ± 0.3 (P ‫ס‬ 0.001) 86 Arc/S 1/100 Biken 1:10 7.4 ± 0.8 (P ‫ס‬ 0.048) 70 7.3 ± 1.9 (P ‫ס‬ 0.95) 100 Repeat experiment 6.8 ± 0.6 (P < 0.001) 93 Arc/S JE (live) 1:2,560 13.0 10 N/A 0 Nonimmune sera <1:20 8.9 ± 1.9 100 7.3 ± 1.5 90 Repeat experiment 9.9 ± 2.1 86 MVE, Murray Valley encephalitis; JE, Japanese encephalitis; ELISA, enzyme-linked immunosorbent assay. N/A, not applicable.…”

Section: Discussionmentioning

confidence: 99%

Immunisation with gamma globulin to Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: Evaluation in a mouse model

et al. 2000

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In northwestern Australia, the flavivirus Murray Valley encephalitis (MVE) poses a significant health risk to infants in some aboriginal communities, particularly during each wet season. While there are too few cases to warrant the development of a vaccine against MVE, a safe, effective prophylaxis for these children is still urgently required. The use of passive transfer of human gamma globulin to MVE or immunisation with a vaccine to the closely related Japanese encephalitis (JE) virus were investigated as potential strategies. When 40 microg of IgG was purified from MVE-immune human sera and transferred to 3-week-old mice, the animals were protected from lethal IP inoculation with MVE virus while still producing a detectable immune response to the virus. Similarly, sera from adult mice infected sublethally with MVE or JE virus provided significant protection against MVE infection. However, sera from mice sublethally infected with the related Kunjin or immunised with the inactivated JE vaccine (Biken) provided no protection against MVE challenge. In fact, mice immunised passively with the latter appeared to succumb to MVE challenge more rapidly than mice that received serum from unimmunised animals, suggesting that antibody to the vaccine had accelerated the progression of disease. These preliminary trials in mice indicate that passive immunisation with human gamma globulin has the greatest potential as a strategy for MVE prophylaxis, whilst the apparent enhancement of MVE by antibodies to the JE vaccine requires further investigation, with particular reference to current vaccination programs in areas of Australia and Papua New Guinea, where both JE and MVE occur.

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Section: Discussionmentioning

confidence: 99%

Immunisation with gamma globulin to Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: Evaluation in a mouse model

et al. 2000

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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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“…Replication-deficient rAd has been used extensively for genetic vaccination (26)(27)(28)(29)(30) or boosting of primed immune responses (31). We have recently shown that intranasal (i.n.)…”

mentioning

confidence: 99%

Intranasal Adenovirus-Vectored Vaccine for Induction of Long-Lasting Humoral Immunity-Mediated Broad Protection against Influenza in Mice

Kim

Park

Han

et al. 2014

J Virol

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Influenza vaccines aimed at inducing antibody (Ab) responses against viral surface hemagglutinin (HA) and neuraminidase (NA) provide sterile immunity to infection with the same subtypes. Vaccines targeting viral conserved determinants shared by the influenza A viruses (IAV) offer heterosubtypic immunity (HSI), a broad protection against different subtypes. We proposed that vaccines targeting both HA and the conserved ectodomain of matrix protein 2 (M2e) would provide protection against infection with the same subtype and also HSI against other subtypes. We report here that single intranasal immunization with a recombinant adenovirus (rAd) vector encoding both HA of H5 virus and M2e (rAdH5/M2e) induced significant HA-and M2e-specific Ab responses, along with protection against heterosubtypic challenge in mice. The protection is superior compared to that induced by rAd vector encoding either HA (rAdH5), or M2e (rAdM2e). While protection against homotypic H5 virus is primarily mediated by virus-neutralizing Abs, the cross-protection is associated with Abs directed to conserved stalk HA and M2e that seem to have an additive effect. Consistently, adoptive transfer of antisera induced by rAdH5/M2e provided the best protection against heterosubtypic challenge compared to that provided by antisera derived from mice immunized with rAdH5 or rAdM2e. These results support the development of rAd-vectored vaccines encoding both H5 and M2e as universal vaccines against different IAV subtypes. IMPORTANCECurrent licensed influenza vaccines provide protection limited to the infection with same virus strains; therefore, the composition of influenza vaccines has to be revised every year. We have developed a new universal influenza vaccine that is highly efficient in induction of long-lasting cross-protection against different influenza virus strains. The cross-protection is associated with a high level of vaccine-induced antibodies against the conserved stalk domain of influenza virus hemagglutinin and the ectodomain of matrix protein. The vaccine could be used to stimulate cross-protective antibodies for the prevention and treatment of influenza with immediate effect for individuals who fail to respond to or receive the vaccine in due time. The vaccine offers a new tool to control influenza outbreaks, including pandemics.

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Immunological basis for protection in a murine model of tick-borne encephalitis by a recombinant adenovirus carrying the gene encoding the NS1 non-structural protein.

Cited by 37 publications

References 38 publications

Immunisation with gamma globulin to Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: Evaluation in a mouse model

Immunisation with gamma globulin to Murray Valley encephalitis virus and with an inactivated Japanese encephalitis virus vaccine as prophylaxis against Australian encephalitis: Evaluation in a mouse model

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

Intranasal Adenovirus-Vectored Vaccine for Induction of Long-Lasting Humoral Immunity-Mediated Broad Protection against Influenza in Mice

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