Experimental Measles. I. Pathogenesis in the Normal and the Immunized Host (original) (raw)
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Journal of Infectious …, 1999
Measles remains a major cause of childhood mortality, with questions about virus virulence and pathogenesis still requiring answers. Rhesus macaques were infected with 5 different culture-adapted strains of measles virus, including 2 from patients with progressive vaccineinduced disease, and a sixth nonculture-adapted strain, Bilthoven. All caused infection detectable by reverse transcriptase-polymerase chain reaction and induction of antibody. Chicago-1 and Bilthoven induced viremias detectable by leukocyte cocultivation. Bilthoven induced Koplik's spots, conjunctivitis, and rash. Lymphopenia and depressed interleukin (IL)-2 production were followed by monocytosis and eosinophilia. All monkeys, including 41 involved in a primate facility outbreak, showed suppressed responses to phytohemagglutinin. As the rash resolved production of IL-2, IL-1b, tumor necrosis factor-a, IL-6, and IL-5 mRNA increased. Monkeys are useful for studies of measles immunopathogenesis, but virus strains must be carefully chosen. Increased virulence of vaccine strains isolated from immunocompromised infants with fatal infections was not evident.
Journal of General Virology, 2007
Both rhesus and cynomolgus macaques have been used as animal models for measles vaccination and immunopathogenesis studies. A number of studies have suggested that experimental measles virus (MV) infection induces more-characteristic clinical features in rhesus than in cynomolgus monkeys. In the present study, both macaque species were infected with two different wild-type MV strains and clinical, virological and immunological parameters were compared. The viruses used were a genotype C2 virus isolated in The Netherlands in 1991 (MV-Bil) and a genotype B3 virus isolated from a severe measles case in Sudan in 1997 (MV-Sudan). Following infection, all rhesus monkeys developed a skin rash and conjunctivitis, which were less obvious in cynomolgus monkeys. Fever was either mild or absent in both species. Virus reisolation profiles from peripheral blood mononuclear cells and broncho-alveolar lavage cells and the kinetics of MV-specific IgM and IgG responses were largely identical in the t...
Immune responses against measles virus in cynomolgus monkeys
Comparative Immunology, Microbiology and Infectious Diseases, 2008
Measles virus (MV) induces profound suppression of the immune response during and for weeks after acute infection. On the other hand, virus-specific immune responses that mediate viral clearance and confer long-lasting immunity are efficiently generated. To investigate this paradox, we studied the immune responses to MV using a monkey model of acute measles. Cynomolgus monkeys were experimentally infected with wild-type MV (MV-HL) and showed marked leukopenia associated with a steady reduction in CD4+ T cell numbers for 18 days post-inoculation. Transient expression of interferon and IL-6 were observed in the serum between 4 and 6 days post-inoculation, and IL-10 levels increased after 11 days postinoculation. Interestingly, IL-8 showed a three-peak increase that correlated with an increase
JCI Insight
Recovery from measles results in lifelong protective immunity. To understand induction of long-28 term immunity, rhesus macaques were studied for six months after infection with WT measles 29 virus (MeV). Infection caused viremia and rash with clearance of infectious virus by 14 days. 30 MeV RNA persisted in PBMCs for 30-90 days and in lymphoid tissue for 6 months most often in 31 B cells but was rarely detected in BM. Antibody with neutralizing activity and binding specificity 32 for MeV nucleocapsid (N), hemagglutinin (H) and fusion proteins appeared with the rash and 33 avidity matured over 3-4 months. Lymph nodes had increasing numbers of MeV-specific 34 antibody-secreting cells (ASCs) and germinal centers with late hyalinization. ASCs appeared in 35 circulation with the rash and continued to appear along with peripheral Tfh cells for the study 36 duration. ASCs in lymph nodes and PBMCs produced antibody to both H and N, with more H-37 specific ASCs in BM. From 14-21 days 20-100-fold more total ASCs than MeV-specific ASCs 38 appeared in circulation suggesting mobilization of pre-existing ASCs. Therefore, persistence of 39 MeV RNA in lymphoid tissue was accompanied by continued germinal center formation, ASC 40 production, avidity maturation and accumulation of H-specific ASCs in BM to sustain 41
Role of CD8+ Lymphocytes in Control and Clearance of Measles Virus Infection of Rhesus Monkeys
Journal of Virology, 2003
The creation of an improved vaccine for global measles control will require an understanding of the immune mechanisms of measles virus containment. To assess the role of CD8 ؉ cytotoxic T lymphocytes in measles virus clearance, rhesus monkeys were depleted of CD8 ؉ lymphocytes by monoclonal anti-CD8 antibody infusion and challenged with wild-type measles virus. The CD8 ؉ lymphocyte-depleted animals exhibited a more extensive rash, higher viral loads at the peak of virus replication, and a longer duration of viremia than did the control antibody-treated animals. These findings indicate a central role for CD8 ؉ lymphocytes in the control of measles virus infections and the importance of eliciting a cell-mediated immune response in new measles vaccine strategies.
Vaccine, 2002
Although the currently used live attenuated measles vaccines are safe and effective, they are dependent on cold chain maintenance and are often ineffective in young infants due to interference by maternal antibody. Therefore, besides vector-based vaccines, different new generation non-replicating candidate measles vaccines are being considered, including nucleic acid vaccines. We have vaccinated cynomolgus macaques transdermally with DNA plasmids encoding measles virus (MV) proteins. Following two vaccinations, low serum antibody responses were detected. Wild-type measles virus challenge 1 year after vaccination showed reduced viraemia in some animals. However, accelerated humoral-and cellular-immune responses were observed in all vaccinated macaques, demonstrating successful priming by the DNA vaccines.
Journal of Virology, 2000
Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.
Measles: A Highly Infectious Viral Zooanthroponosis of Public Health Concern
Viral diseases, such as Nipah virus, Covid-19, monkeypox, swine flu, Hendra virus, avian influenza, rabies, yellow fever, Rift Vally fever, and others are important cause of morbidity as well as mortality in humans and animals worldwide. Measles is one most devastating viral disease that is responsible to infect around 20 million people globally every year. Measles virus is more infectious than influenza virus. The incidence of measles is higher in children than adults, and outbreaks of disease usually occur in early spring and late winter. Disease can spread rapidly unless the herd immunity is sustained. Hitherto, humans are known as the only natural host of measles, and can infect the monkeys. Clinical symptoms including cough, coryza and conjunctivitis are observed in most of the cases. Laboratory tests, such as immunofluorescence, virus isolation, immunological and molecular tools can be useful to make an unequivocal diagnosis of disease. Since there are no antiviral chemotherapeutic agents are available to treat the sick persons, immunization is the mainstay to control the disease as it provides a lasting immunity of about two decades.
Experimental Measles. II. Infection and Immunity in the Rhesus Macaque
Virology, 1997
... Yong-de Zhu a , Janet Heath b , Jennifer Collins a , Todd Greene a ... 11. ML Cohn, ED Robinson, M. Faerber, D. Thomas, S. Geyer, S. Peters, M. Martin, A. Martin, D. Sobel, R. Jones, L. Larkin and JR Richert, Measles vaccine failures: Lack of sustained measles-specific ...