Detection of Cellular Immunity to Rabies Antigens in Human Vaccinees

Moore, Susan M.; Wilkerson, Melinda J.; Davis, Rolan D.; Wyatt, Carol R.; Briggs, Deborah J.

doi:10.1007/s10875-006-9044-0

Cited by 44 publications

(30 citation statements)

References 19 publications

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“…The longevity of the protective immune response might need booster immunizations with the ORFV recombinant, at least in mice or as earlier reported in rats (51). The findings that groups of animals showed different survival rates but comparable VNA titers indicate that apart from humoral immunity, additional cellular immune mechanisms contribute to protection, particularly the induction and activation of T lymphocytes, including their cytokine production (8,65). The presented in vivo depletion experiments supported the importance of CD4-positive T cells for protection after application of D1701-V-RabG.…”

Section: Discussionmentioning

confidence: 69%

“…immunizations of 10 5 PFU, 10 6 PFU, or 10 7 PFU of D1701-V-RabG. Sera were collected at 2,5,8,11,14,17,20, and 40 weeks after prime immunization, and mice were i.c. challenged with 100 LD 50 at week 43 and observed for an additional 28 days.…”

Section: Resultsmentioning

confidence: 99%

“…Protection against rabies correlates with the presence of VNA, which persists for many years, and VNA titers greater than 0.5 IU per ml serum are accepted for protection. Accordingly, rabies can be considered a T-helper type 2 cell responsive disease, and the help of CD4-positive T cells to activate B cells is crucial for protection (8).…”

mentioning

confidence: 99%

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A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

Amann

Rohde

Wulle

et al. 2013

J Virol

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The present study describes the generation of a new Orf virus (ORFV) recombinant, D1701-V-RabG, expressing the rabies virus (RABV) glycoprotein that is correctly presented on the surface of infected cells without the need of replication or production of infectious recombinant virus. One single immunization with recombinant ORFV can stimulate high RABV-specific virus-neutralizing antibody (VNA) titers in mice, cats, and dogs, representing all nonpermissive hosts for the ORFV vector. The protective immune response against severe lethal challenge infection was analyzed in detail in mice using different dosages, numbers, and routes for immunization with the ORFV recombinant. Long-term levels of VNA could be elicited that remained greater than 0.5 IU per ml serum, indicative for the protective status. Single applications of higher doses (10 7 PFU) can be sufficient to confer complete protection against intracranial (i.c.) challenge, whereas booster immunization was needed for protection by the application of lower dosages. Anamnestic immune responses were achieved by each of the seven tested routes of inoculation, including oral application. Finally, in vivo antibody-mediated depletion of CD4-positive and/or CD8-posititve T cell subpopulations during immunization and/or challenge infection attested the importance of CD4 T cells for the induction of protective immunity by D1701-V-RabG. This report demonstrates another example of the potential of the ORFV vector and also indicates the capability of the new recombinant for vaccination of animals.

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Section: Discussionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 99%

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A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

Amann

Rohde

Wulle

et al. 2013

J Virol

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“…Based on their FSC and SSC properties, proliferating cells were defined as described by others [28][29][30]. The proliferation index (PI), a measure of the frequency of cells that have gone through more than three divisions (positive proliferation, CFSE low ), was assessed using a software program (Summit version 6.0) [28][29][30]. The final PI was calculated as the ratio of the average PI for antigen-stimulated cells to the average PI for unstimulated cells.…”

Section: Flow Cytometric Analysismentioning

confidence: 99%

A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection

Melgaço

Morgado

Santiago³

et al. 2015

Vaccine

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Based on current studies on the effects of single dose vaccines on antibody production, Latin American countries have adopted a single dose vaccine program. However, no data are available on the activation of cellular response to a single dose of hepatitis A. Our study investigated the functional reactivity of the memory cell phenotype after hepatitis A virus (HAV) stimulation through administration of the first or second dose of HAV vaccine and compared the response to that of a baseline group to an initial natural infection. Proliferation assays showed that the first vaccine dose induced HAV-specific cellular response; this response was similar to that induced by a second dose or an initial natural infection. Thus, from the first dose to the second dose, increase in the frequencies of classical memory B cells, TCD8 cells, and central memory TCD4 and TCD8 cells were observed. Regarding cytokine production, increased IL-6, IL-10, TNF, and IFNγ levels were observed after vaccination. Our findings suggest that a single dose of HAV vaccine promotes HAV-specific memory cell response similar to that induced by a natural infection. The HAV-specific T cell immunity induced by primary vaccination persisted independently of the protective plasma antibody level. In addition, our results suggest that a single dose immunization system could serve as an alternative strategy for the prevention of hepatitis A in developing countries.

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“…The proliferating cells (R1 + R2) were defined based on their FSC and SSC properties[28]. The proliferation index (PI) was determined by the software program; this index is a measure of the frequency of cells that have gone through more than three divisions (positive proliferation, CFSE low ) (Figure 1C and D)[28-30]. The final PI was determined by calculating the ratio of the average PI for mitogen- or antigen-stimulated cells divided by the average PI of unstimulated cells (Figure 1).…”

Section: Methodsmentioning

confidence: 99%

Changes in cellular proliferation and plasma products are associated with liver failure

Melgaço¹,

Soriani²,

Sucupira³

et al. 2016

WJH

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AIMTo study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis.METHODSForty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced self-limited AH and ALF. Thus, we worked with five groups: Hepatitis A virus (HAV)-induced self-limited acute hepatitis (HAV-AH), HAV-induced ALF (HAV-ALF), non-viral-induced self-limited acute hepatitis (non-viral AH), non-viral-induced acute liver failure (non-viral ALF), and healthy subjects (HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.RESULTSThe levels of mitochondrial DNA (mtDNA) and the cytokines investigated [interleukin (IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology (P < 0.05). High plasma mtDNA and IL-10 were the best markers associated with ALF [mtDNA: OR = 320.5 (95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8 (95%CI: 1.38-257.94), P = 0.028] and death [mtDNA: OR = 12.1 (95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01 (95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NKbright, NKT and regulatory T cells (TReg) predominated in virus-specific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature.CONCLUSIONmtDNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.

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Detection of Cellular Immunity to Rabies Antigens in Human Vaccinees

Cited by 44 publications

References 19 publications

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection

Changes in cellular proliferation and plasma products are associated with liver failure

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