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164 results on '"Milich, David R."'

5. Palivizumab epitope-displaying virus-like particles protect rodents from RSV challenge

Author

Schickli, Jeanne H., Whitacre, David C., Tang, Roderick S., Kaur, Jasmine, Lawlor, Heather, Peters, Cory J., Jones, Joyce E., Peterson, Darrell L., McCarthy, Michael P., Van Nest, Gary, and Milich, David R.

Subjects
Palivizumab -- Health aspects, Antigenic determinants -- Health aspects, Gene therapy -- Innovations, Respiratory syncytial virus -- Prevention, Health care industry
Abstract

Respiratory syncytial virus (RSV) is the most common cause of serious viral bronchiolitis in infants, young children, and the elderly. Currently, there is not an FDA-approved vaccine available for RSV, though the mAb palivizumab is licensed to reduce the incidence of RSV disease in premature or at-risk infants. The palivizumab epitope is a well-characterized, approximately 24-aa helix-loop-helix structure on the RSV fusion (F) protein (F254-277). Here, we genetically inserted this epitope and multiple site variants of this epitope within a versatile woodchuck hepadnavirus core-based virus-like particle (WHcAg- VLP) to generate hybrid VLPs that each bears 240 copies of the RSV epitope in a highly immunogenic arrayed format. A challenge of such an epitope-focused approach is that to be effective, the conformational F254-277 epitope must elicit antibodies that recognize the intact virus. A number of hybrid VLPs containing RSV F254-277 were recognized by palivizumab in vitro and elicited high-titer and protective neutralizing antibody in rodents. Together, the results from this proof-of-principle study suggest that the WHcAg-VLP technology may be an applicable approach to eliciting a response to other structural epitopes., Introduction Reverse vaccinology has accelerated the identification of new antigenic epitopes on infectious agents, tumors, and allergens, and has fueled the concept of epitope-focused vaccine design. However, the conversion of [...]

Published
2015
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21. Role of B cells in antigen presentation of the hepatitis B core

Author

Milich, David R., Chen, Margaret, Schodel, Florian, Peterson, Darrell L., Jones, Joyce E., and Hughes, Janice L.

Subjects
Antigen presenting cells -- Research, B cells -- Research, Hepatitis associated antigen -- Research, Science and technology
Abstract

The hepatitis B virus (HBV) nucleocapsid or core antigen (HBcAg) is extremely immunogenic during infection and after immunization. For example, during many chronic infections, HBcAg is the only antigen capable of eliciting an immune response, and nanogram amounts of HBcAg elicit antibody production in mice. Recent structural analysis has revealed a number of characteristics that may help explain this potent immunogenicity. Our analysis of how the HBcAg is presented to the immune system revealed that the HBcAg binds to specific membrane Ig (mIg) antigen receptors on a high frequency of resting, murine B cells sufficiently to induce B7.1 and B7.2 costimulatory molecules. This enables HBcAg-specific B cells from unprimed mice to take up, process, and present HBcAg to naive Th cells in vivo and to T cell hybridomas in vitro approximately [10.sup.5] times more efficiently than classical macrophage or dendritic antigen-presenting cells (APC). These results reveal a structure-function relation for the HBcAg, confirm that B cells can function as primary APC, explain the enhanced immunogenicity of HBcAg, and may have relevance for the induction and/or maintenance of chronic HBV infection.

Published
1997

26. Importance of subtype in the immune response to the pre-S(2) region of the hepatitis B surface antigen: II. Synthetic pre-S(2) immunogen

Author

Milich, David R., Jones, Joyce E., McLachlan, Alan, Bitter, Grant, Moriarty, Ann, and Hughes, Janice L.

Subjects
Peptides -- Usage, Hepatitis B -- Physiological aspects, Major histocompatibility complex -- Physiological aspects, Vaccines -- Research, Health
Abstract

There are four major subtypes of hepatitis B virus (HBV). To ensure responsiveness to the various subtypes of HBV, a vaccine should include the pre-S(2) region of the hepatitis B surface antigen (HBsAg), located on the outer coat of the virus, from the two major subtypes of HBV, subtypes d and y. The ability of an individual to respond to pre-S(2) depends on the histocompatibility antigens of the individual. The major histocompatibility complex (MHC) encodes proteins, which distinguish foreign from non-foreign agents in the body and allow an immune response to occur. T cells recognize antigen as a complex with the proteins of the MHC. There are many types of MHC molecules, and antigens can be recognized by T cells with only certain types of MHC. A peptide was made in the laboratory that combined the two sites of the pre-S(2) subunit which are important in the generation of an immune response, the sites that are recognized by T cells and those that are recognized by B cells. The peptide contained the site that was recognized by T cells in most of the strains of mice tested. This synthetic peptide produced an antibody response when tested in various strains of mice with different MHC antigens, but there were variations in what was being recognized by the antibody. Therefore, the use of synthetic peptides for vaccine development is complicated and further research is needed to understand the cellular interactions that occur for the development of immunity against hepatitis B in humans. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

27. Importance of subtype in the immune response to the pre-s(2) region of the hepatitis B surface antigen: I. T cell fine specificity

Author

Milich, David R., Hughes, Janice L., McLachlan, Alan, Langley, Keith E., Thornton, George B., and Jones, Joyce E.

Subjects
Vaccines -- Research, Hepatitis B -- Physiological aspects, Cellular immunity -- Physiological aspects, Major histocompatibility complex -- Physiological aspects, T cells -- Physiological aspects, Health
Abstract

The hepatitis B surface antigen (HBsAg) is present on three proteins of hepatitis B virus (HBV) envelope. Various sites on the HBsAg elicit immune responses and portions of the proteins are being used to develop vaccines against hepatitis B. There are four major subtypes of HBV. A study was conducted to see if T cells could recognize differences in the various subtypes of virus in the HBsAg region known as pre-S(2). T cells recognize antigen as a complex with the proteins of the major histocompatibility complex (MHC). The MHC encodes proteins, which distinguish foreign from non-foreign agents in the body. There are many types of MHC molecules, and antigens can be recognized by T cells with only certain of the types of MHC. Consequently, the ability of T cells to recognize the viral subtypes of the HBsAg with certain MHC in various strains of mice was also examined. It was shown that T cells recognize differences in the four subtypes of HBV in a certain region of the pre-S(2) subunit. Vaccines that are developed against HBV must include the region of the pre-S2 subunit from at least the two major subtypes of HBV, subtypes d and y, to ensure that an immune response is made against the various subtypes of HBV. Vaccines that are currently being used in clinical trials are comprised of only one subunit. There were differences in which MHC molecules could combine with the subunits, indicating that there will be individual variability in humans who respond to the molecules. These findings provide additional evidence that the pre-S2 subunit from the various subtypes should be included in HBV vaccine, as more people will be able to respond to the different types of antigens. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1990

31. Identification of a unique double-negative regulatory T-cell population

Author

Lee, Byung O, Jones, Joyce E, Peters, Cory J, Whitacre, David, Frelin, Lars, Hughes, Janice, Kim, Won-Keun, and Milich, David R

Subjects
CD8 Antigens, Interleukin-2 Receptor alpha Subunit, Receptors, Antigen, T-Cell, hemic and immune systems, chemical and pharmacologic phenomena, Forkhead Transcription Factors, Mice, Transgenic, Original Articles, Lymphocyte Activation, T-Lymphocytes, Regulatory, Immunophenotyping, Mice, T-Lymphocyte Subsets, Glucocorticoid-Induced TNFR-Related Protein, CD4 Antigens, Animals, Interleukin-2, Hepatitis B e Antigens, Cell Proliferation
Abstract

Regulatory T (Treg) cells represent one of the main mechanisms of regulating self-reactive immune cells. Treg cells are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery. Although the function of Treg cells has been demonstrated in many experimental settings, the precise mechanisms and antigen specificity often remain unclear. In a hepatitis B e antigen-T-cell receptor (HBeAg-TCR) double transgenic mouse model, we observed a phenotypically unique (TCR+) CD4- /CD8- CD25(+/-) GITR(high) PD-1(high) FoxP3-) HBeAg-specific population that demonstrates immune regulatory function. This HBeAg-specific double-negative regulatory cell population proliferates vigorously in vitro, in contrast to any other known regulatory population, in an interleukin-2-independent manner.

Published
2011

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