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Biomedical subjects

C A Cannon

Publications and source records attributed to C A Cannon.

13 recordsLinked to original sources

Factors influencing cellular immune responses to feline immunodeficiency virus induced by DNA vaccination.

Virus-specific effector cytotoxic T lymphocytes (CTL) were elicited in the peripheral blood of domestic cats following a single intramuscular inoculation of replication defective feline immunodeficiency virus proviral DNA (FIVDeltaRT). Higher levels of virus-specific cytolysis were observed in the blood when cats were co-inoculated with feline gamma-interferon (IFN) DNA. The responses declined by 12 weeks following the first DNA inoculation and were, with the exception of FIV Gag-specific responses in some cats, refractory to repeated DNA inoculations. Nevertheless, a significant proportion of the cats were protected from challenge with homologous virus. The effects of interval between inoculations, route of DNA delivery, and promoter used to regulate viral gene expression on the induction of virus-specific CTLs were evaluated. The highest levels of virus-specific lysis were recorded following intramuscular co-inoculation of FIVDeltaRT and gamma-IFN DNA, where FIV gene expression was under the control of a cytomegalovirus (CMV) promoter. However, the highest levels of protection were observed using the viral 5'LTR as the promoter. These results suggest that a single intramuscular inoculation of FIVDeltaRT DNA together with gamma-IFN DNA may be sufficient to induce virus-specific CTLs and protection.

Animals↗

Suppression of feline immunodeficiency virus replication in vitro by a soluble factor secreted by CD8+ T lymphocytes.

Mitogen-activated lymphoblasts isolated from the blood and lymph nodes, but not the spleen, of domestic cats acutely infected with the Petaluma or Glasgow8 isolates of feline immunodeficiency virus (FIV), suppressed the replication of FIV in the MYA-1 T-cell line in a dose-dependent manner. This effect was not limited to the homologous isolate of FIV. The suppressor activity declined with progression to chronic infection, with lower levels of activity detectable only in the lymph nodes. Immunization of domestic cats with whole inactivated FIV vaccine elicited profound suppressor activity in both the blood and lymph nodes. The suppressor activity was associated with the CD8+ T-cell subpopulation, the effect did not appear to be major histocompatibility complex-restricted, and was mediated by a soluble factor(s). This activity may be associated with the control of virus replication during both the asymptomatic stages of FIV infection, and in the protective immunity observed in cats immunized with whole inactivated virus vaccines.

Acute Disease↗

Vaccination with a feline immunodeficiency virus multiepitopic peptide induces cell-mediated and humoral immune responses in cats, but does not confer protection.

Cats were immunized with a 46-residue multiepitopic synthetic peptide of feline immunodeficiency virus (FIV) comprising immunodominant epitopes present in the third variable domain of the envelope glycoprotein, transmembrane glycoprotein (TM), and p24 Gag core protein, using Quil A as an adjuvant. All vaccinated cats developed a humoral response which recognized the synthetic peptide immunogen and the intact viral core and envelope proteins. A FIV Gag- and Env-specific effector cytotoxic T-lymphocyte response was also detected in the peripheral blood of vaccinated cats, which peaked at week 30. This response appeared to be major histocompatibility complex restricted. Epitope mapping studies revealed that both the cellular and humoral immune responses were directed principally to a peptide within the TM glycoprotein, CNQNQFFCK. However, vaccination did not confer protection when cats were challenged with the Petaluma isolate of FIV at week 35.

Adjuvants, Immunologic↗

Suppression of virus burden by immunization with feline immunodeficiency virus Env protein.

Whole inactivated virus (WIV) vaccines derived from the FLA cell line protect cats against challenge with feline immunodeficiency virus (FIV). To discover whether the protective effects of WIV could be reproduced by the isolated Env component, either WIV or immunoaffinity-purified FIV gp120 from the FL4 cell line was administered to cats. Although both vaccines induced high levels of virus neutralizing antibodies, purified Env was much less effective than WIV in protecting cats against viraemia. However, reduced virus load in PBMCs was evident in all Env-immunized cats compared to controls. Analyses of antibody responses to bacterial expression products of FIV Env, which were high in Env-immunized cats but low in animals receiving the WIV vaccine, suggested that the partially denatured, monomeric Env induces a less effective antiviral immune response than WIV. Hence, the superior immunogenicity of WIV may be due to the presentation of the native oligomeric structure of Env on virions.

Animals↗

Involvement of gag- and env-specific cytotoxic T lymphocytes in protective immunity to feline immunodeficiency virus.

Definition of the immunological mechanisms involved in protective immunity against lentiviral infections is crucial to the development of an effective vaccine. The induction of gag- and env-specific cell-mediated immune responses was studied in cats following vaccination with whole inactivated feline immunodeficiency virus (FIV). Cats were immunized by inoculation with three doses of paraformaldehyde-inactivated FIV, derived from the feline lymphoid cell line, FL-4, which is persistently infected with the Petaluma isolate of FIV. Autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag- or env-vaccinia virus or pulsed with FIV env peptides were used as targets in chromium-51 release assays. Effector cells were fresh peripheral blood mononuclear cells. Following the third immunization, all vaccinated cats, but none of the control cats immunized with adjuvant alone, had detectable FIV env-specific lymphocytotoxicity in their peripheral blood. Two cats also exhibited gag-specific activity. There was no recognition of either allogeneic skin fibroblasts infected with recombinant vaccinia virus or autologous target cells infected with wild-type vaccinia virus, indicating the specificity and MHC-restricted nature of the response. Vaccinated cats, but not control cats, were protected from challenge with the homologous Petaluma isolate of FIV. Partial epitope mapping of the env-specific cytotoxic response was performed using overlapping 10-amino acid peptides from the env V3 domain of FIV. This response appeared to be directed at env peptide 1 (RAISSWKQRN) and env peptide 3 (QRNRWEWRPD), which lie adjacent to a beta-turn within the V3 domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Induction of feline immunodeficiency virus-specific cell-mediated and humoral immune responses following immunization with a multiple antigenic peptide from the envelope V3 domain.

Cytotoxic T-cell determinants should be an important component of a vaccine against feline immunodeficiency virus (FIV). Epitope mapping studies have revealed an immunodominant neutralization epitope within the third variable (V3) domain of the viral envelope glycoprotein comprizing 17 amino acids (residues 390-406: RAISSWKQRNRWEWRPD). We have investigated the induction of FIV-specific cytotoxicity and anti-peptide antibody in cats immunized with a multiple antigenic peptide (MAP) containing this epitope. Virus-specific lymphocytotoxicity was determined using autologous or allogeneic skin fibroblasts as target cells labelled with chromium-51 and pulsed with overlapping 10 amino acid peptides. Cytotoxic effector cells derived from fresh peripheral blood were detected in five out of 10 immunized cats. The cell-mediated immune response appeared to be directed to envelope peptide 1 (RAISSWKQRN) and peptide 2 (SWKQRNRWEW), with recognition of peptide 3 (QRNRWEWRPD) in only one cat. An antibody response to the 17 amino acid peptide immunogen was detected in seven immunized cats, which was directed to envelope peptides 2 and 3. These results suggest that different epitopes may be recognized by the cell-mediated and humoral immune responses. None of the cats was protected from challenge with the Glasgow8 isolate of FIV (FIV/GL-8). This study has implications for vaccine strategies using synthetic peptides to induce virus-specific cell-mediated immune responses.

Amino Acid Sequence↗

Induction of feline immunodeficiency virus-specific cytotoxic T cells in vivo with carrier-free synthetic peptide.

The role of cellular immunity in the establishment and progression of immunosuppressive lentivirus infection remains equivocal. To develop a model system with which these aspects of the host immune response can be studied experimentally, we examined the response of cats to a hybrid peptide containing predicted T-and B-cell epitopes from the gag and env genes of feline immunodeficiency virus (FIV). Cats were immunized with an unmodified 17-residue peptide incorporating residues 196 to 208 (from gag capsid protein p24) and 395 to 398 (from env glycoprotein gp120) of the FIV Glasgow-8 strain by using Quil A as an adjuvant. Virus-specific lymphocytotoxicity was measured by chromium-51 release assays. The target cells were autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag vaccinia virus or pulsed with FIV peptides. Effector cells were either fresh peripheral blood mononuclear cells or T-cell lines stimulated with FIV peptides in vitro. Cytotoxic effector cells from immunized cats lysed autologous, but not allogeneic, target cells when they were either infected with recombinant FIV gag vaccinia virus or pulsed with synthetic peptides comprising residues 196 to 205 or 200 to 208 plus 395. Depletion of CD8+ T cells, from the effector cell population abrogated the lymphocytotoxicity. Immunized cats developed an antibody response to the 17-residue peptide immunogen and to recombinant p24. However, no antibodies which recognized smaller constituent peptides could be detected. This response correlated with peptide-induced T-cell proliferation in vitro. This study demonstrates that cytotoxic T lymphocytes specific for FIV can be induced following immunization with an unmodified short synthetic peptide and defines a system in which the protective or pathological role of such responses can be examined.

Amino Acid Sequence↗

Polyclonal B-cell activation in cats infected with feline immunodeficiency virus.

The specificity of the antibody response following natural or experimental infection of domestic cats with feline immunodeficiency virus (FIV) was examined. The antibody response to a range of non-viral antigens, including trinitrophenol (TNP), ovalbumin, beta-galactosidase, deoxyribonucleic acid (DNA) and keyhole limpet haemocyanin (KLH), was measured in 220 cats naturally infected with FIV. Infected cats had higher antibody levels to these antigens, in particular TNP, KLH and beta-galactosidase, than non-infected control cats. Competition binding studies demonstrated that this response was not due to the presence of cross-reacting epitopes on recombinant FIV p17 or p24 antigens, suggesting that the B-cell activation associated with infection was polyclonal rather than entirely virus specific. Studies on cats experimentally infected with FIV revealed a similar pattern, with infected cats developing an antibody response to heterologous non-viral antigens at 6-8 weeks post-infection. There were two discernible peaks of antibody activity, the first occurring 10-20 weeks post-infection and the second peak 40-60 weeks post-infection. The antibody response to KLH, DNA and beta-galactosidase remained elevated throughout the 90-week study period, whereas the antibody levels to the other antigens declined to levels approaching those observed in normal cats.

Animals↗

The whys of patient education.

The rationale for patient education is that patients and families have the right to be informed; that professional standards describe appropriate patient education; that health care organizations and the law require patient education; and patients, health care organizations, and that society benefit from the process. Patients with cancer benefit in terms of knowledge acquisition, enhanced self-care, reduced anxiety, enhanced self-concept and self-esteem, increased satisfaction with care, improved pain control, improved oral status, and reduced disruption in daily functioning. Health care organizations benefit in terms of quality services, reduced costs, and reduction in malpractice suits. Society benefits as patients with knowledge and skills maintain or resume functional status and return to school, work, or service activities. Nurses are key professionals in the coordination and delivery of patient education programs. They too have the opportunity to benefit from patient education through therapeutic alliances with patients and families that foster both personal and professional satisfaction.

Economics, Hospital↗

Analysis of human antibody response to cholera vaccination by Epstein Barr virus transformation and human-human hybridoma production.

The response of Epstein Barr virus transformable B lymphocytes to V. cholerae serotypes Inaba and Ogawa was assessed at various periods of time after primary and secondary immunization. In both cases, 100% of cells laid down at 10(4)/well gave a very strong positive reaction with either serotype one week after immunization. Further analysis indicated that general polyclonal activation by the bacterial LPS was not a major feature since the reactivity with other bacterial antigens was weak. Human monoclonal antibodies generated from the primary wells by backfusion with the KR4 cell line had low affinity in comparison to rat monoclonal antibodies reactive with the same antigen but were serotype specific and able to fix guinea pig complement.

Animals↗

A statewide assessment of preferences of registered nurses desiring academic credit-bearing continuing education.

As needs, mandates, and interests for continuing education (CE) in nursing increase, institutions of higher learning have growing opportunities and responsibilities to respond. Planning educational programs necessitates assessment of nurses' needs to deliver offerings responsive to topic, delivery method, and scheduling preferences. This nonrandomized statewide telephone survey of 535 registered nurses describes the preferences of the large subgroup (n = 359) of nurses who stated a desire for academic credit while participating in CE programs. Preferences were further examined in relation to the nurses' eligibility for undergraduate or master's level offerings. Results include a number of specific preferences with implications for educational institutions to increase their creativity and flexibility in developing credit CE offerings, and to become more responsive to the needs of nurses in practice. Findings suggest that partnerships between institutions of higher education and health care may better meet the continuing education needs of nurses.

Choice Behavior↗

Preparing for mandatory continuing education--assessing interests.

Assessment of needs is the foundation of nursing practice as well as nursing education. To increase responsivity to the continuing education (CE) needs of registered nurses (RNs) within a small, yet diverse, mid-Atlantic state in which CE was recently mandated for relicensure, a telephone survey was used to gather information on a large nonrandomized sample of RNs. Preferences for types of programming, methods and locations for acquiring CE, scheduling, academic credit in addition to CE credit, and an automated service for maintaining CE attendance records were identified. This study presents an overview of survey results helpful in planning offerings most likely to attract and satisfy nurses.

Adult↗