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    C1 Vaccines
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    Abstract:
    Vaccines are the most commonly administered immunotherapeutics. Supported by great improvements in sanitation facilities such as safe drinking water, vaccination was the most effective measure to control a diversity of life-threatening infectious diseases in the 20th century. The most impressive success of vaccination was the global eradication of smallpox in the 1970s. Moreover, the incidence of many other infectious diseases, such as diphtheria, tetanus, pertussis, poliomyelitis, measles, mumps, and rubella, has been drastically reduced thanks to extensive vaccination programmes.
    The envelope (E) glycoprotein of JEV is the major antigen to elicit neutralizing antibody (NAb) against JEV infection. In order to develop a rapid and safe neutralization assay system for evaluation of the JEV vaccine strains, we constructed JEV-pseudotyped viruses with JEV env genes (Nakayama-NIH, Beijing-1). The titers of JEV-pseudotyped viruses with NK and BJ strains were 4.0×104 IFU/ml and 1.3×105 IFU/ml in Vero cell cultures, respectively. We have analyzed the neutralization activity of immunized mouse sera with JEV-NK and JEV-BJ pseudotyped viruses. The neutralizing antibody titers of NK and BJ (50% reduction of virus) were about 1:10,000 at each immunized sera. Compared with conventional plaque reduction neutralization test (PRNT), the method using JEV-pseudotyped virus has desirable advantages such as more rapid, easier, and non-biohazardous. This neutralization assay system might be useful to evaluate NAb activity against JEV vaccine strains or vaccine candidates.
    Vero cell
    Citations (0)
    Infectious clone technology provides an opportunity to study the molecular basis of arthropod–virus interactions in detail. This study describes the development of an infectious clone of the prototype yellow fever virus Asibi strain (YFV-As) with the purpose of identifying sequences or domains that influence infection dynamics in the mosquito vector. The full-length cDNA of YFV-As virus was produced from RT-PCR products of parental viral RNA. These were cloned into a low-copy-number plasmid previously used to develop the YFV-17D infectious clone (pACNR/FLYF-17D). Virus recovered from the infectious clone exhibited biological characteristics similar to those of the parental YFV-As, including replication kinetics, reactivity to flavivirus cross-reactive and YFV-specific antibodies and infection and dissemination rates in Aedes aegypti , the principal mosquito vector of YFV. These data provide the basis for future studies with chimeric Asibi/17D viruses to identify the determinants of vaccine attenuation in the vector.
    clone (Java method)
    Flavivirus
    Citations (41)
    Herpes B virus infects naturally monkeys of the macaque genus in whom it can cause recurrent oral and genital lesions. However, when the virus infects humans it causes a neurological illness with a high case fatality rate. Successful treatment is possible but this depends on diagnosis prior to the onset of respiratory arrest, and fatalities over the last 10 years have been the result of late or no diagnostic data on which to base anti-viral intervention. An effective vaccine would be an ideal way to combat the risk of herpes B virus disease in humans working with potentially infected monkeys or their tissues. A recombinant vaccinia virus expressing herpes B virus glycoprotein D (gD) was constructed and rabbits inoculated with the chimeric virus were tested for immunoglobulin responses to herpes B virus by virus neutralisation, ELISA and Western blot analyses. Anti-gD humoral responses were detected in all vaccinated animals by ELISA and Western blot but neutralising antibody was not detected prior to challenge with herpes B virus. Non-vaccinated rabbits died within 8 days of challenge while 10/11 vaccinated animals were protected against herpes B virus disease. No antibodies to herpes B virus proteins other than gD were detectable in surviving animals, suggesting minimal herpes B virus replication post challenge. Autopsies were carried out on 4/10 rabbits which had remained healthy at 31 days post challenge and the dorsal root ganglia adjacent to the inoculation site were removed. Attempts to detect herpes B virus DNA by PCR followed by hybridisation proved negative suggesting protection against latent herpes B virus infection. J. Med. Virol. 57:47–56, 1999. © 1999 Wiley-Liss, Inc.
    Recombinant virus
    Orthopoxvirus
    Poxviridae
    Abstract Experimental rotavirus infection was investigated in pigtailed macaques to study the infectivity, immunity, and pathogenesis of rotavirus. A challenge virus, YK‐1, was administered intragastrically to four seronegative macaques (age: 11–16 months). Although none of the monkeys developed diarrhea, an active infection occurred with high titers of rotavirus antigen detected in stools 2–10 days after challenge. These animals developed rotavirus‐specific antibody responses similar to those seen following primary exposure to rotavirus. YK‐1 was then inoculated in four seropositive macaques (age: 14–16 months). All animals shed viral antigen in their stool, but the titers and duration were significantly less when compared to seronegative macaques. When rechallenged 28 days after initial YK‐1 challenge, the macaques demonstrated significant protection against reinfection. All seropositive animals developed a rise in rotavirus‐specific serum and fecal antibodies during YK‐1 challenge and rechallenge. To independently assess the role of age and preexisting IgG titers to rotavirus, a 4‐month‐old seronegative and 6‐month‐old seropositive macaque were inoculated with YK‐1. The seronegative macaque shed high titers of virus for 9 days, while the seropositive macaque shed only 3 days and in low titer. These data suggest that a primate model of rotavirus infection using the YK‐1 strain may be useful in examining the immune response and protection from infection in pigtailed macaques and indicate that levels and duration of shedding may provide a good measure of protection from natural infection and from that induced by oral or parenteral vaccines. J. Med. Virol. 75:616–625, 2005. Published 2005 Wiley‐Liss, Inc.
    Simian
    Simian immunodeficiency virus
    Haplorhini
    Rotavirus Infections
    Citations (13)
    The ability of a live attenuated simian immunodeficiency virus (SIV) to protect against challenge with cloned SIVmac251/BK28 was evaluated in four cynomolgus macaques. The intravenous infection of the C8 variant of the SIVmac251/32H virus, carrying an in-frame 12 bp deletion in the nef gene, did not affect the CD4 and CD8 cell counts, and a persistent infection associated with an extremely low virus burden in peripheral blood mononuclear cells (PBMCs) was established. After 40 weeks, these monkeys were challenged intravenously with a 50 MID50 dose of SIVmac251/BK28 virus grown on macaque cells. Four naive monkeys were infected as controls. Monkeys were monitored for 62 weeks following challenge. Attempts to rescue virus from either PBMCs or bone marrow from the C8-vaccin- ated monkeys were unsuccessful, but in two cases virus was re-isolated from lymph node cells. The presence of the SIV provirus with the C8 variant genotype maintaining its original nef deletion was shown by differential PCR in PBMCs, lymph nodes and bone marrow. Furthermore, in contrast to the control monkeys, the vaccinated monkeys showed normal levels for CD4M and CD8M cells, minimal lymphoid hyperplasia and no clinical signs of infection. Our results confirm that vaccination with live attenuated virus can confer protection. This appears to be dependent on the ability of the C8 variant to establish a persistent but attenuated infection which is necessary for inducing an immune response, as suggested by the persistence of a strong immune B cell memory and by the over-expression of interleukin (IL)-2, interferon-γ and IL-15 mRNAs in PBMCs of C8-vaccinated monkeys but not in those of control monkeys.
    Simian immunodeficiency virus
    Simian
    African Green Monkey
    SUMMARY A recombinant vaccinia virus strain which contains and expresses a 26S cDNA insert encoding Sindbis virus structural proteins (VV:3S) was used to infect a continuous line of Aedes albopictus mosquito cells. There were not visible cytopathic effects due to the virus infection and the cells continued to grow normally. However, examination of the proteins present in the cytoplasm of the infected cells with Sindbis virus-specific antisera revealed that Sindbis virus proteins were being synthesized and processed. These results are discussed with respect to (i) vaccinia virus as a non-lethal expression vector to deliver and express eukaryotic genetic information in insect cell systems and (ii) using this system (VV:3S) to dissect various facets of togavirus-insect cell interactions.
    Recombinant virus
    Togaviridae
    Orthopoxvirus