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1.
Soc Work Public Health ; 38(2): 147-160, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35895505

RESUMO

Social workers play an integral role in hospitals, particularly as it relates to improving patient outcomes. This scoping review was conducted to explore the impact of social work interventions in hospital settings on healthcare utilization. Research literature was identified using the following search engines: PsycINFO, CINAHL Plus, SocINDEX & MEDLINE. The initial search was conducted in May 2019, and an updated search was conducted in April 2021. Search results identified 2633 references and 110 articles met criteria for full-text review. Eighteen articles were included in the final review. Social work interventions include transitional care (56%), care coordination (22%), behavioral health (17%) and case management (5%). Significant improvements to readmission, mortality and utilizations rates are reported in over 80% of the studies, however the vast majority are non-randomized quantitative studies. More rigorous studies are needed to expand the literature and further evaluate the effectiveness of social work interventions in hospital settings.


Assuntos
Hospitais , Assistentes Sociais , Humanos , Serviço Social
2.
Soc Work Health Care ; 61(5): 353-368, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35736662

RESUMO

Social needs are factors for health risk and depression that may negatively impact health outcomes and costly services use. Care management addresses social needs that can reduce health risk and depression. An exploratory study of the 5-step Ambulatory Integration of the Medical and Social Model (AIMS) was conducted to examine the effect of steps completed as part of AIMS on patients' depression and health risk outcomes at 6-months. Results reveal steps central to AIMS are significantly related to lower depression and health risk, suggesting AIMS is a valuable intervention for reducing health risk and depression.


Assuntos
Depressão , Depressão/terapia , Humanos
3.
Soc Work Health Care ; 60(2): 197-207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33775235

RESUMO

Covid-19 has profoundly impacted social work and has exposed the existing inequities in the health care system in the United States. Social workers play a critical role in the pandemic response for historically marginalized communities and for those who find themselves needing support for the first time. Innovative approaches to care management, including the Center for Health and Social Care Integration (CHaSCI) Bridge Model of transitional care provides a foundation from which social workers can rise to meet these new challenges.


Assuntos
COVID-19/epidemiologia , Atenção à Saúde/organização & administração , Múltiplas Afecções Crônicas/epidemiologia , Administração dos Cuidados ao Paciente/organização & administração , Serviço Social/organização & administração , Idoso , Idoso de 80 Anos ou mais , Humanos , Relações Interinstitucionais , Serviços de Saúde Mental/organização & administração , Pandemias , Assistência Centrada no Paciente/organização & administração , SARS-CoV-2 , Autogestão , Telemedicina/organização & administração , Estados Unidos/epidemiologia
4.
Soc Work Health Care ; 60(4): 334-353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657981

RESUMO

Social needs, which are social risk factors including lack of access to stable housing, healthy food, or reliable transportation, are recognized as integral to health. Free clinics tend to serve patients with social needs, yet, few are screened or receive assistance. Lack of personnel, resources, and procedures to identify and assist patients are reasons few free clinics consider social needs. To address this service gap, a midwestern free clinic and neighboring Masters of Social Work (MSW) program established a partnership. A social needs screen was developed and integrated into health care practice. An MSW intern was also embedded as a member of the health care team to provide social needs assistance. A 6-month pilot study was conducted to assess the value of the screen and use of MSW assistance services. Of the 223 patients screened, 66.4% (n = 146) scored positive for social needs. Only four percent (n = 6) of the patients used MSW services. Chi-square analyses reveal significant differences in social needs by age, gender, race, education, and primary language. The findings suggest that the screening and MSW intern services are valuable; however, they further suggest that screening alone may be insufficient to encourage utilization of MSW services.


Assuntos
Instituições de Assistência Ambulatorial , Programas de Rastreamento , Habitação , Humanos , Projetos Piloto , Meios de Transporte
6.
Prof Case Manag ; 24(6): 306-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31580298

RESUMO

PURPOSE OF THE STUDY: The purpose of this study was to examine the time contribution of social workers in delivering AIMS (Ambulatory Integration of the Medical and Social), a care management protocol designed to address patients' nonmedical needs, and the association of time contribution with patients' depression outcomes. PRIMARY PRACTICE SETTING: The study was conducted in 6 primary care provider clinics housed in a large, urban academic medical center located in the Midwestern United States. METHODOLOGY AND SAMPLE: A longitudinal, quasi-experimental study employing survey procedures and a retrospective review of patient records was conducted. The study included 340 patients 50 years and older with unmet nonmedical needs. Half of the patients received AIMS, which was delivered by social workers. The other half received usual care (UC), which was delivered by other health care providers. RESULTS: Chi-square analysis and independent-samples t tests were performed to compare time spent addressing nonmedical needs with differences in patients' depression levels at 6 months postenrollment. The findings reveal that social workers spend significantly more time with patients than UC providers addressing patients' nonmedical needs (p < .0001). At 6 months postintervention, reduced levels of depression were observed for AIMS patients when compared with UC patients (p = .026). IMPLICATIONS FOR CARE MANAGEMENT PRACTICE: Including social workers as part of health care teams is valuable. Time spent with patients and engaging in care management activities to support patients' needs is linked with positive health outcomes. Given the benefits of care management, opportunities for reimbursement are enhanced.


Assuntos
Pessoal de Saúde/organização & administração , Pessoal de Saúde/estatística & dados numéricos , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/estatística & dados numéricos , Assistentes Sociais/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos , Estudos Retrospectivos , Inquéritos e Questionários
7.
J Am Geriatr Soc ; 67(S2): S412-S418, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31074858

RESUMO

The medical, psychological, cognitive, and social needs of older adults with serious illness are best met by coordinated and team-based services and support. These services are best provided in a seamless care model anchored by integrated biopsychosocial assessments focused on what matters to older adults and their social determinants of health; individualized care plans with shared goals; care provision and management; and quality measurement with continuous improvement. This model requires (1) racially and ethnically diverse healthcare professionals, including mental health and direct service workers, with training in aging and team collaboration; (2) an integrated network of community-based organizations (CBOs) providing in-home services; (3) an electronic communication platform that spans the system of providers and organizations with skilled technology staff; and (4) payment models that incentivize team-based care across the continuum of services, including CBOs, with adequate salaries and academic loan forgiveness to recruit and retain high-quality team members. Assuring that this model is effective requires ongoing quality assurance measures that include not only quality of care and utilization data to demonstrate cost offsets of service integration, but also quality of life for both the older adults and the family members caring for them. Although this may seem a lofty ideal in comparison with our current fragmented system, we review models that provide the key elements effectively and cost efficiently. We then propose an Essential Care Model that defines best practice in meeting the needs of older adults with serious illness and their families. J Am Geriatr Soc 67:S412-S418, 2019.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Serviços de Saúde para Idosos/organização & administração , Vida Independente , Modelos Organizacionais , Equipe de Assistência ao Paciente/organização & administração , Recursos Humanos/normas , Idoso , Humanos , Múltiplas Afecções Crônicas/terapia , Determinantes Sociais da Saúde
8.
Soc Work Health Care ; 58(1): 93-107, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30590995

RESUMO

While behavioral health symptoms commonly present in primary care, most primary care providers lack the time, resources, and expertise to identify and treat them on their own. To address this need, many quality improvement efforts are underway to expand teams and integrate behavioral health assessments and interventions into primary care. Due to their expertise in behavioral health, community supports, and behavioral activation, social workers are natural leaders in integrating care. This paper describes one urban academic medical center's efforts to ensure adolescent and adult patients with depressive symptoms are connected to adequate care and support. A case study is included to demonstrate the Collaborative Care Team model as described, including details regarding the role social workers play. Key quality improvement and policy considerations for scaling up and sustaining collaborative initiative are included.


Assuntos
Administração de Caso/organização & administração , Depressão/terapia , Serviços de Saúde Mental/organização & administração , Atenção Primária à Saúde/organização & administração , Serviço Social/organização & administração , Centros Médicos Acadêmicos , Comportamento Cooperativo , Depressão/diagnóstico , Feminino , Humanos , Masculino , Equipe de Assistência ao Paciente/organização & administração , Melhoria de Qualidade/organização & administração , Estados Unidos
9.
Vaccine ; 27(10): 1549-56, 2009 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-19168105

RESUMO

Modified Vaccinia Ankara (MVA) is a replication-defective strain of vaccinia virus (VV) that is being investigated in humans as an alternative vaccine against smallpox. Understanding the parameters of a MVA vaccine regimen that can effectively enhance protective immunity will be important for clinical development. The present studies utilize cohorts of rhesus monkeys immunized with recombinant MVA (rMVA) or recombinant VV (rVV) vaccine vectors to investigate the magnitude, breadth, and durability of anti-VV immunity elicited by a single or multi-dose vaccine regimen. These data demonstrate that a single immunization with rMVA elicits weaker cellular and humoral immunity compared to a single inoculation with rVV. However, vaccine-elicited antibody responses, but not T cell responses, are significantly enhanced with repeated immunizations of rMVA. Importantly, only monkeys receiving up to four inoculations with rMVA generated neutralizing antibody (NAb) responses that were comparable in magnitude and durability to those elicited in monkeys receiving two inoculations with rVV. These data also show that the breadth of antibody responses against protein antigens associated with two antigenically distinct forms of infectious VV are similar in rMVA- and rVV-immunized monkeys. Together, these studies suggest that a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates robust and durable antibody-mediated immunity comparable to that elicited by replication-competent VV.


Assuntos
Vacina Antivariólica/administração & dosagem , Vaccinia virus/imunologia , Vacinas Virais/administração & dosagem , Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Animais , Anticorpos Antivirais/biossíntese , Antígenos Virais/genética , Reações Cruzadas , Vírus Defeituosos/genética , Vírus Defeituosos/imunologia , Vírus da Varíola das Aves Domésticas/genética , Vírus da Varíola das Aves Domésticas/imunologia , Vetores Genéticos , Humanos , Imunidade Celular , Imunização Secundária , Macaca mulatta , Testes de Neutralização , Vacina Antivariólica/genética , Vacina Antivariólica/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vaccinia virus/genética , Vacinas Virais/genética , Vacinas Virais/imunologia
10.
J Virol ; 82(14): 6829-37, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18448519

RESUMO

The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia virus challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing L1R-specific neutralizing antibodies afforded postexposure prophylaxis after systemic vaccinia virus infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia virus challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia virus challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines.


Assuntos
Vacina Antivariólica/imunologia , Varíola/imunologia , Varíola/prevenção & controle , Vaccinia virus/imunologia , Adenoviridae/genética , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/uso terapêutico , Peso Corporal , Quimioprevenção/métodos , Vírus da Ectromelia/genética , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Vacina Antivariólica/genética , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia
11.
J Virol ; 82(10): 4844-52, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18337575

RESUMO

Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-gamma(+)) and IFN-gamma(+)/tumor necrosis factor alpha(+) (TNF-alpha(+)) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2(+) (IL-2(+)) and polyfunctional IFN-gamma(+)/TNF-alpha(+)/IL-2(+) T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8(+) and CD4(+) T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.


Assuntos
Adenoviridae/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vetores Genéticos/imunologia , Vacinas contra a SAIDS/imunologia , Animais , Produtos do Gene gag/genética , Produtos do Gene gag/imunologia , Imunização/métodos , Imunização Secundária/métodos , Interferon gama/biossíntese , Interleucina-2/biossíntese , Macaca mulatta , Fator de Necrose Tumoral alfa/biossíntese
12.
J Virol ; 81(9): 4654-63, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17329340

RESUMO

Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.


Assuntos
Infecções por Adenoviridae/epidemiologia , Adenoviridae/genética , Vetores Genéticos/genética , Vacinas Sintéticas/genética , Vacinas Virais/genética , Infecções por Adenoviridae/sangue , África Subsaariana/epidemiologia , Animais , Sequência de Bases , Clonagem Molecular , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Vetores Genéticos/imunologia , Humanos , Macaca mulatta , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Testes de Neutralização , Análise de Sequência de DNA , Estudos Soroepidemiológicos , Sorotipagem
13.
J Virol ; 80(24): 12009-16, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17035318

RESUMO

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have been constructed from Ad subgroup B, including rAd11 and rAd35, as well as from Ad subgroup D, including rAd49. However, the optimal combination of vectors for heterologous rAd prime-boost vaccine regimens and the extent of cross-reactive vector-specific neutralizing antibodies (NAbs) remain poorly defined. We have shown previously that the closely related vectors rAd11 and rAd35 elicited low levels of cross-reactive NAbs. Here we show that these cross-reactive NAbs correlated with substantial sequence homology in the hexon hypervariable regions (HVRs) and suppressed the immunogenicity of heterologous rAd prime-boost regimens. In contrast, vectors with lower hexon HVR homology, such as rAd35 and rAd49, did not elicit detectable cross-reactive vector-specific NAbs. Consistent with these findings, rAd35-rAd49 vaccine regimens proved more immunogenic than both rAd35-rAd5 and rAd35-rAd11 regimens in mice with anti-Ad5 immunity. These data suggest that optimal heterologous rAd prime-boost regimens should include two vectors that are both rare in human populations to circumvent preexisting antivector immunity as well as sufficiently immunologically distinct to avoid cross-reactive antivector immunity.


Assuntos
Adenoviridae/imunologia , Reações Cruzadas/imunologia , Vetores Genéticos/imunologia , Vacinas Sintéticas/imunologia , Adenoviridae/genética , Animais , Anticorpos/imunologia , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Técnicas Imunoenzimáticas , Camundongos , Camundongos Endogâmicos C57BL , Testes de Neutralização
14.
J Virol ; 80(24): 11991-7, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17005652

RESUMO

Generating broad cellular immune responses against a diversity of viral epitopes is a major goal of current vaccine strategies for human immunodeficiency virus type 1 (HIV-1) and other pathogens. Virus-specific CD8(+) T-lymphocyte responses, however, are often highly focused on a very limited number of immunodominant epitopes. For an HIV-1 vaccine, the breadth of CD8(+) T-lymphocyte responses may prove to be critical as a result of the need to cover a wide diversity of viral isolates in the population and to limit viral escape from dominant epitope-specific T lymphocytes. Here we show that epitope modification strategies can alter CD8(+) T-lymphocyte epitope immunodominance hierarchies elicited by a DNA vaccine in mice. Mice immunized with a DNA vaccine expressing simian immunodeficiency virus Gag lacking the dominant D(b)-restricted AL11 epitope generated a marked and durable augmentation of responses specific for the subdominant D(b)-restricted KV9 epitope. Moreover, anatomic separation strategies and heterologous prime-boost regimens generated codominant responses against both epitopes. These data demonstrate that dominant epitopes can dramatically suppress the immunogenicity of subdominant epitopes in the context of gene-based vaccines and that epitope modification strategies can be utilized to enhance responses to subdominant epitopes.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Produtos do Gene gag/imunologia , Imunidade Celular/imunologia , Epitopos Imunodominantes/imunologia , Vacinas contra a SAIDS/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Epitopos de Linfócito T/genética , Feminino , Imunidade Celular/genética , Epitopos Imunodominantes/genética , Técnicas Imunoenzimáticas , Camundongos , Camundongos Endogâmicos C57BL , Vacinas contra a SAIDS/genética
15.
Nature ; 441(7090): 239-43, 2006 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-16625206

RESUMO

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy.


Assuntos
Adenoviridae/genética , Adenoviridae/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Engenharia Genética , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Adenoviridae/classificação , Adenoviridae/fisiologia , Animais , Linfócitos T CD8-Positivos/imunologia , DNA Recombinante/genética , Terapia Genética , Macaca mulatta/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Testes de Neutralização , Vacinas
16.
J Virol ; 79(22): 14161-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16254351

RESUMO

Preexisting immunity to adenovirus serotype 5 (Ad5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. A potential solution to this problem is to utilize rAd vectors derived from rare Ad serotypes, such as Ad35. However, rAd35 vectors have appeared less immunogenic than rAd5 vectors in preclinical studies to date. In this study, we explore the hypothesis that the differences in immunogenicity between rAd5 and rAd35 vectors may be due in part to differences between the fiber proteins of these viruses. We constructed capsid chimeric rAd35 vectors containing the Ad5 fiber knob (rAd35k5) and compared the immunogenicities of rAd5, rAd35k5, and rAd35 vectors expressing simian immunodeficiency virus Gag and HIV-1 Env in mice and rhesus monkeys. In vitro studies demonstrated that rAd35k5 vectors utilized the Ad5 receptor CAR rather than the Ad35 receptor CD46. In vivo studies showed that rAd35k5 vectors were more immunogenic than rAd35 vectors in both mice and rhesus monkeys. These data suggest that the Ad5 fiber knob contributes substantially to the immunogenicity of rAd vectors. Moreover, these studies demonstrate that capsid chimeric rAd vectors can be constructed to combine beneficial immunologic and serologic properties of different Ad serotypes.


Assuntos
Infecções por Adenoviridae/imunologia , Adenoviridae/imunologia , Proteínas do Capsídeo/genética , Vacinas Virais , Adenoviridae/classificação , Adenoviridae/genética , Animais , Epitopos/química , Epitopos/imunologia , Imunização , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Sorotipagem , Replicação Viral
17.
J Virol ; 79(15): 9694-701, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16014931

RESUMO

The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-Ad5 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.


Assuntos
Adenovírus Humanos/imunologia , Vetores Genéticos/imunologia , Vírus Reordenados/imunologia , Vacinas Virais/imunologia , Animais , Formação de Anticorpos , Reações Cruzadas , Avaliação Pré-Clínica de Medicamentos , Produtos do Gene gag/genética , Terapia Genética , Imunidade Celular , Imunização Secundária , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos C57BL , Vírus da Imunodeficiência Símia/genética , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem
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