Immunogens of encephalitis viruses

Roehrig, John T.

doi:10.1016/0378-1135(93)90029-7

Cited by 14 publications

(5 citation statements)

References 60 publications

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“…Given the WEEV evolutionary history, WEEV E1ecto may be an efficient antigen for developing cross- protective antibodies among NWA and OWA species. Finally, monoclonal antibodies against E1 (McMillan strain) are alphavirus group reactive (36)(37)(38). The insect cell-derived McMillan E1ecto antigen presented to mice in the LANAC context (CLNC-ODN-PIC) may explain why our study differs from a previous study that immunized mice with recombinant bacterium-derived WEEV E1 antigen and reported minimal protection against two WEEV strains (3).…”

Section: Discussionmentioning

confidence: 99%

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

Phillips

Schountz

Toth

et al. 2014

J Virol

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Alphaviruses are mosquito-borne viruses that cause significant disease in animals and humans. Western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV), two New World alphaviruses, can cause fatal encephalitis, and EEEV is a select agent of concern in biodefense. However, we have no antiviral therapies against alphaviral disease, and current vaccine strategies target only a single alphavirus species. In an effort to develop new tools for a broader response to outbreaks, we designed and tested a novel alphavirus vaccine comprised of cationic lipid nucleic acid complexes (CLNCs) and the ectodomain of WEEV E1 protein (E1ecto). Interestingly, we found that the CLNC component, alone, had therapeutic efficacy, as it increased survival of CD-1 mice following lethal WEEV infection. Immunization with the CLNC-WEEV E1ecto mixture (lipid-antigennucleic acid complexes [LANACs]) using a prime-boost regimen provided 100% protection in mice challenged with WEEV subcutaneously, intranasally, or via mosquito. Mice immunized with LANACs mounted a strong humoral immune response but did not produce neutralizing antibodies. Passive transfer of serum from LANAC E1ecto-immunized mice to nonimmune CD-1 mice conferred protection against WEEV challenge, indicating that antibody is sufficient for protection. In addition, the LANAC E1ecto immunization protocol significantly increased survival of mice following intranasal or subcutaneous challenge with EEEV. In summary, our LANAC formulation has therapeutic potential and is an effective vaccine strategy that offers protection against two distinct species of alphavirus irrespective of the route of infection. We discuss plausible mechanisms as well the potential utility of our LANAC formulation as a pan-alphavirus vaccine.

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Section: Discussionmentioning

confidence: 99%

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

Phillips

Schountz

Toth

et al. 2014

J Virol

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“…For IFA, monoclonal antibody (MAb) A8 directed against EHV-1 glycoprotein M (gM) was used to detect EHV-1 infection, and MAb1A3B-7, which is directed against VEEV E2 and is reactive with a conformation-dependent epitope within the neutralization domain, was routinely used for detection of expression of VEEV structural proteins. 32,35,36 The RK13 cells were seeded in six-well-plates and infected with either H⌬gp2 or rH_VEEV virus at a multiplicity of infection (MOI) of 0.0001. One hour postinfection, medium was removed and infected cells were over-laid with 0.25% methylcellulose in EMEM-10% FBS.…”

Section: Indirect Immunofluorescence Analysis (Ifa) Andmentioning

confidence: 99%

Protection of Mice by Equine Herpesvirus Type 1–Based Experimental Vaccine against Lethal Venezuelan Equine Encephalitis Virus Infection in the Absence of Neutralizing Antibodies

Rosas

Paessler

et al. 2008

The American Journal of Tropical Medicine and Hygiene

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A vectored vaccine based on equine herpesvirus type 1 (EHV-1) was generated as an alternative for safe and efficient prophylaxis against Venezuelan equine encephalitis virus (VEEV) infection. Two-step (en passant) Red mutagenesis was used to insert VEEV structural genes into an infectious clone of EHV-1 vaccine strain RacH. The recombinant virus, rH_VEEV, efficiently and stably expressed VEEV structural proteins as detected by various antibodies, including a conformation-dependent monoclonal antibody to envelope glycoprotein E2. In addition, rH_VEEV was indistinguishable from parental bacterial artificial chromosome-derived virus with respect to growth properties in cultured cells. Immunization of mice with the vectored vaccine conferred full protection against lethal challenge infection using VEEV strain ZPC738 in the absence of neutralizing antibodies and in a dose-dependent manner. Analyses of IgG responses demonstrated production of VEEV-specific IgG1 and total IgG antibodies after vaccination, indicating that protection was dependent on either cytotoxic T cell responses or antibody-mediated protection unrelated to neutralizing activity.

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“…However, they are not useful for serological screening and epidemiological studies based on serocomplex‐ or virus‐specific seroconversion because they do not persist long enough. There are numerous cross‐reacting, serocomplex‐ and virus‐specific epitopes within the viral structural proteins (Hunt and Roehrig, 1985; Roehrig et al., 1990; Roehrig, 1993) which account for the extensive cross‐reactions observed in either CF or HI tests (O.I.E., 2000). As with virus‐specific IgM antibodies, CF antibodies do not persist very long and thus are not useful in approaches other than the confirmation of suspected clinical cases.…”

Section: Introductionmentioning

confidence: 99%

Detection of Antibodies to Alphaviruses and Discrimination between Antibodies to Eastern and Western Equine Encephalitis Viruses in Rabbit Sera using a Recombinant Antigen and Virus‐specific Monoclonal Antibodies

Pässler

Pfeffer²

2003

Journal of Veterinary Medicine, Series B

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Three arthropod-borne alphaviruses, western equine encephalitis viruses (WEEV), eastern equine encephalitis viruses (EEEV) and Venezuelan equine encephalitis viruses are the aetiological agents of a sometimes severe encephalomyelitis in equines and humans in the New World. With regard to the different ecology and epidemiology of these viruses, a method applied in serological screening should be able to distinguish between them as well as other related members of the genus Alphavirus in the American continent. However, this has been hampered in the past by (a) the close antigenic relationship between alphaviruses in traditional serological assays, especially in the routinely used haemagglutination-inhibition, and (b) the need of biosafety level 3 facilities to grow the viral antigens. An epitope blocking assay using an EEEV glycoprotein E1-expressing recombinant Sindbis virus and virus-specific monoclonal antibodies (mAbs) binding to the E1 of EEEV (strain NJ/60) and the E1 of Sindbis virus was established using automated flow cytometry. The test was evaluated using sera of infected and vaccinated rabbits. A cut-off value of 30% inhibition for antigenic complex-specific seroconversion was found to be sufficient for the detection of the respective infection. By using three different mAbs in parallel, we were able to detect alphavirus genus-, EEEV- and WEEV-complex-specific serum antibodies. As this test is based on the inhibition of binding of virus-specific mAbs, sera of every origin other than mouse can be tested. Thus, this assay may prove useful in the serological screening of a variety of animal species during an outbreak investigation.

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Immunogens of encephalitis viruses

Cited by 14 publications

References 60 publications

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

Liposome-Antigen-Nucleic Acid Complexes Protect Mice from Lethal Challenge with Western and Eastern Equine Encephalitis Viruses

Protection of Mice by Equine Herpesvirus Type 1–Based Experimental Vaccine against Lethal Venezuelan Equine Encephalitis Virus Infection in the Absence of Neutralizing Antibodies

Detection of Antibodies to Alphaviruses and Discrimination between Antibodies to Eastern and Western Equine Encephalitis Viruses in Rabbit Sera using a Recombinant Antigen and Virus‐specific Monoclonal Antibodies

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