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1.
PLoS Med ; 17(3): e1003024, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32181756

RESUMO

BACKGROUND: The Vaxxas high-density microarray patch (HD-MAP) consists of a high density of microprojections coated with vaccine for delivery into the skin. Microarray patches (MAPs) offer the possibility of improved vaccine thermostability as well as the potential to be safer, more acceptable, easier to use, and more cost-effective for the administration of vaccines than injection by needle and syringe (N&S). Here, we report a phase I trial using the Vaxxas HD-MAP to deliver a monovalent influenza vaccine that was to the best of our knowledge the first clinical trial to evaluate the safety, tolerability, and immunogenicity of lower doses of influenza vaccine delivered by MAPs. METHODS AND FINDINGS: HD-MAPs were coated with a monovalent, split inactivated influenza virus vaccine containing A/Singapore/GP1908/2015 H1N1 haemagglutinin (HA). Between February 2018 and March 2018, 60 healthy adults (age 18-35 years) in Melbourne, Australia were enrolled into part A of the study and vaccinated with either: HD-MAPs delivering 15 µg of A/Singapore/GP1908/2015 H1N1 HA antigen (A-Sing) to the volar forearm (FA); uncoated HD-MAPs; intramuscular (IM) injection of commercially available quadrivalent influenza vaccine (QIV) containing A/Singapore/GP1908/2015 H1N1 HA (15 µg/dose); or IM injection of H1N1 HA antigen (15 µg/dose). After 22 days' follow-up and assessment of the safety data, a further 150 healthy adults were enrolled and randomly assigned to 1 of 9 treatment groups. Participants (20 per group) were vaccinated with HD-MAPs delivering doses of 15, 10, 5, 2.5, or 0 µg of HA to the FA or 15 µg HA to the upper arm (UA), or IM injection of QIV. The primary objectives of the study were safety and tolerability. Secondary objectives were to assess the immunogenicity of the influenza vaccine delivered by HD-MAP. Primary and secondary objectives were assessed for up to 60 days post-vaccination. Clinical staff and participants were blind as to which HD-MAP treatment was administered and to administration of IM-QIV-15 or IM-A/Sing-15. All laboratory investigators were blind to treatment and participant allocation. Two further groups in part B (5 participants per group), not included in the main safety and immunological analysis, received HD-MAPs delivering 15 µg HA or uncoated HD-MAPs applied to the forearm. Biopsies were taken on days 1 and 4 for analysis of the cellular composition from the HD-MAP application sites. The vaccine coated onto HD-MAPs was antigenically stable when stored at 40°C for at least 12 months. HD-MAP vaccination was safe and well tolerated; any systemic or local adverse events (AEs) were mild or moderate. Observed systemic AEs were mostly headache or myalgia, and local AEs were application-site reactions, usually erythema. HD-MAP administration of 2.5 µg HA induced haemagglutination inhibition (HAI) and microneutralisation (MN) titres that were not significantly different to those induced by 15 µg HA injected IM (IM-QIV-15). HD-MAP delivery resulted in enhanced humoral responses compared with IM injection with higher HAI geometric mean titres (GMTs) at day 8 in the MAP-UA-15 (GMT 242.5, 95% CI 133.2-441.5), MAP-FA-15 (GMT 218.6, 95% CI 111.9-427.0), and MAP-FA-10 (GMT 437.1, 95% CI 254.3-751.3) groups compared with IM-QIV-15 (GMT 82.8, 95% CI 42.4-161.8), p = 0.02, p = 0.04, p < 0.001 for MAP-UA-15, MAP-FA-15, and MAP-FA-10, respectively. Higher titres were also observed at day 22 in the MAP-FA-10 (GMT 485.0, 95% CI 301.5-780.2, p = 0.001) and MAP-UA-15 (367.6, 95% CI 197.9-682.7, p = 0.02) groups compared with the IM-QIV-15 group (GMT 139.3, 95% CI 79.3-244.5). Results from a panel of exploratory immunoassays (antibody-dependent cellular cytotoxicity, CD4+ T-cell cytokine production, memory B cell (MBC) activation, and recognition of non-vaccine strains) indicated that, overall, Vaxxas HD-MAP delivery induced immune responses that were similar to, or higher than, those induced by IM injection of QIV. The small group sizes and use of a monovalent influenza vaccine were limitations of the study. CONCLUSIONS: Influenza vaccine coated onto the HD-MAP was stable stored at temperatures up to 40°C. Vaccination using the HD-MAP was safe and well tolerated and resulted in immune responses that were similar to or significantly enhanced compared with IM injection. Using the HD-MAP, a 2.5 µg dose (1/6 of the standard dose) induced HAI and MN titres similar to those induced by 15 µg HA injected IM. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR.org.au), trial ID 108 ACTRN12618000112268/U1111-1207-3550.


Assuntos
Imunogenicidade da Vacina , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinação , Administração Cutânea , Adolescente , Adulto , Anticorpos Antivirais/sangue , Austrália , Células Cultivadas , Estabilidade de Medicamentos , Feminino , Humanos , Imunoglobulina A/metabolismo , Vacinas contra Influenza/efeitos adversos , Influenza Humana/imunologia , Influenza Humana/virologia , Injeções Intramusculares , Masculino , Saliva/imunologia , Saliva/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Adesivo Transdérmico , Resultado do Tratamento , Vacinação/efeitos adversos , Adulto Jovem
2.
Vaccines (Basel) ; 11(11)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38006057

RESUMO

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blinded, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18-50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3100 median cell-culture infectious dose [CCID50] measles, ~4300 CCID50 rubella); high-dose MR-HD-MAPs (~9300 CCID50 measles, ~12,900 CCID50 rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1000 CCID50 per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2-8 °C for at least 24 months. When MR HD-MAPs stored at 2-8 °C for 24 months were transferred to 40 °C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates on day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7%, respectively, for measles, and 37.5%, 25.0% and 35.7%, respectively, for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808.

3.
PLoS One ; 16(7): e0255282, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34329337

RESUMO

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier to use and more cost-effective method for administration of vaccines when compared to the needle and syringe. Since MAPs deliver vaccine to the dermis and epidermis, a degree of local immune response at the site of application is expected. In a phase 1 clinical trial (ACTRN 12618000112268), the Vaxxas high-density MAP (HD-MAP) was used to deliver a monovalent, split inactivated influenza virus vaccine into the skin. HD-MAP immunisation led to significantly enhanced humoral responses on day 8, 22 and 61 compared with IM injection of a quadrivalent commercial seasonal influenza vaccine (Afluria Quadrivalent®). Here, the aim was to analyse cellular responses to HD-MAPs in the skin of trial subjects, using flow cytometry and immunohistochemistry. HD-MAPs were coated with a split inactivated influenza virus vaccine (A/Singapore/GP1908/2015 [H1N1]), to deliver 5 µg haemagglutinin (HA) per HD-MAP. Three HD-MAPs were applied to the volar forearm (FA) of five healthy volunteers (to achieve the required 15 µg HA dose), whilst five control subjects received three uncoated HD-MAPs (placebo). Local skin response was recorded for over 61 days and haemagglutination inhibition antibody titres (HAI) were assessed on days 1, 4, 8, 22, and 61. Skin biopsies were taken before (day 1), and three days after HD-MAP application (day 4) and analysed by flow-cytometry and immunohistochemistry to compare local immune subset infiltration. HD-MAP vaccination with 15 µg HA resulted in significant HAI antibody titres compared to the placebo group. Application of uncoated placebo HD-MAPs resulted in mild erythema and oedema in most subjects, that resolved by day 4 in 80% of subjects. Active, HA-coated HD-MAP application resulted in stronger erythema responses on day 4, which resolved between days 22-61. Overall, these erythema responses were accompanied by an influx of immune cells in all subjects. Increased cell infiltration of CD3+, CD4+, CD8+ T cells as well as myeloid CD11b+ CD11c+ and non-myeloid CD11b- dendritic cells were observed in all subjects, but more pronounced in active HD-MAP groups. In contrast, CD19+/CD20+ B cell counts remained unchanged. Key limitations include the use of an influenza vaccine, to which the subjects may have had previous exposure. Different results might have been obtained with HD-MAPs inducing a primary immune response. In conclusion, influenza vaccine administered to the forearm (FA) using the HD-MAP was well-tolerated and induced a mild to moderate skin response with lymphocytic infiltrate at the site of application.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Sistemas de Liberação de Medicamentos , Imunidade Celular/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/administração & dosagem , Pele/imunologia , Adulto , Antígenos CD/imunologia , Feminino , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
4.
Vaccine ; 37(50): 7408-7418, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-29224963

RESUMO

The development of vaccines against herpes simplex virus (HSV) is an important global goal for sexual and reproductive health. A key priority to advance development of HSV vaccines is the definition of preferred product characteristics (PPCs), which provide strategic guidance on World Health Organization (WHO) preferences for new vaccines, specifically from a low- and middle-income country (LMIC) perspective. To start the PPC process for HSV vaccines, the WHO convened a global stakeholder consultation in March 2017, to define the priority public health needs that should be addressed by HSV vaccines and discuss the key considerations for HSV vaccine PPCs, particularly for LMICs. Meeting participants outlined an initial set of overarching public health goals for HSV vaccines in LMICs, which are: to reduce the acquisition of HIV associated with HSV-2 infection in high HIV-prevalence populations and to reduce the burden of HSV-associated disease, including mortality and morbidity due to neonatal herpes and impacts on sexual and reproductive health. Participants also considered the role of prophylactic versus therapeutic vaccines, whether both HSV-2 and HSV-1 should be targeted, important target populations, and infection and disease endpoints for clinical trials. This article summarizes the main discussions from the consultation.


Assuntos
Vacinas contra o Vírus do Herpes Simples/imunologia , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/imunologia , Animais , Herpes Genital/imunologia , Herpes Simples/imunologia , Humanos , Complicações Infecciosas na Gravidez/imunologia , Encaminhamento e Consulta , Organização Mundial da Saúde
5.
Vaccine ; 36(7): 932-938, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29221895

RESUMO

In August 2016, the World Health Organization (WHO) convened the "Eighth meeting on development of influenza vaccines that induce broadly protective and long-lasting immune responses" to discuss the regulatory requirements and pathways for licensure of next-generation influenza vaccines, and to identify areas where WHO can promote the development of such vaccines. Participants included approximately 120 representatives of academia, the vaccine industry, research and development funders, and regulatory and public health agencies. They reviewed the draft WHO preferred product characteristics (PPCs) of vaccines that could address prioritized unmet public health needs and discussed the challenges facing the development of such vaccines, especially for low- and middle-income countries (LMIC). They defined the data desired by public-health decision makers globally and explored how to support the progression of promising candidates into late-stage clinical trials and for all countries. This report highlights the major discussions of the meeting.


Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Ensaios Clínicos como Assunto , Humanos , Vacinas contra Influenza/efeitos adversos , Saúde Pública , Cobertura Vacinal , Organização Mundial da Saúde
6.
Vaccine ; 36(7): 921-931, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29336923

RESUMO

Many industrialized countries have implemented routine immunization policies for older adults, but similar strategies have not been widely implemented in low- and middle-income countries (LMICs). In March 2017, the World Health Organization (WHO) convened a meeting to identify policies and activities to promote access to vaccination of older adults, specifically in LMICs. Participants included academic and industry researchers, funders, civil society organizations, implementers of global health interventions, and stakeholders from developing countries with adult immunization needs. These experts reviewed vaccine performance in older adults, the anticipated impact of adult vaccination programs, and the challenges and opportunities of building or strengthening an adult and older adult immunization platforms. Key conclusions of the meeting were that there is a need for discussion of new opportunities for vaccination of all adults as well as for vaccination of older adults, as reflected in the recent shift by WHO to a life-course approach to immunization; that immunization in adults should be viewed in the context of a much broader model based on an individual's abilities rather than chronological age; and that immunization beyond infancy is a global priority that can be successfully integrated with other interventions to promote healthy ageing. As WHO is looking ahead to a global Decade of Healthy Ageing starting in 2020, it will seek to define a roadmap for interdisciplinary collaborations to integrate immunization with improving access to preventive and other healthcare interventions for adults worldwide.


Assuntos
Envelhecimento/imunologia , Programas de Imunização , Vacinação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Controle de Doenças Transmissíveis , Saúde Global , Humanos , Vacinas , Organização Mundial da Saúde
7.
Vaccine ; 36(26): 3779-3788, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29779922

RESUMO

BACKGROUND: Injection using needle and syringe (N&S) is the most widely used method for vaccination, but requires trained healthcare workers. Fear of needles, risk of needle-stick injury, and the need to reconstitute lyophilised vaccines, are also drawbacks. The Nanopatch (NP) is a microarray skin patch comprised of a high-density array of microprojections dry-coated with vaccine that is being developed to address these shortcomings. Here we report a randomised, partly-blinded, placebo-controlled trial that represents the first use in humans of the NP to deliver a vaccine. METHODS: Healthy volunteers were vaccinated once with one of the following: (1) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 µg haemagglutinin (HA) per dose), applied to the volar forearm (NP-HA/FA), n = 15; (2) NPs coated with split inactivated influenza virus (A/California/07/2009 [H1N1], 15 µg HA per dose), applied to the upper arm (NP-HA/UA), n = 15; (3) Fluvax® 2016 containing 15 µg of the same H1N1 HA antigen injected intramuscularly (IM) into the deltoid (IM-HA/D), n = 15; (4) NPs coated with excipients only, applied to the volar forearm (NP-placebo/FA), n = 5; (5) NPs coated with excipients only applied to the upper arm (NP-placebo/UA), n = 5; or (6) Saline injected IM into the deltoid (IM-placebo/D), n = 5. Antibody responses at days 0, 7, and 21 were measured by haemagglutination inhibition (HAI) and microneutralisation (MN) assays. FINDINGS: NP vaccination was safe and acceptable; all adverse events were mild or moderate. Most subjects (55%) receiving patch vaccinations (HA or placebo) preferred the NP compared with their past experience of IM injection with N&S (preferred by 24%). The antigen-vaccinated groups had statistically higher HAI titres at day 7 and 21 compared with baseline (p < 0.0001), with no statistical differences between the treatment groups (p > 0.05), although the group sizes were small. The geometric mean HAI titres at day 21 for the NP-HA/FA, NP-HA/UA and IM-HA/D groups were: 335 (189-593 95% CI), 160 (74-345 95% CI), and 221 (129-380 95% CI) respectively. A similar pattern of responses was seen with the MN assays. Application site reactions were mild or moderate, and more marked with the influenza vaccine NPs than with the placebo or IM injection. INTERPRETATION: Influenza vaccination using the NP appeared to be safe, and acceptable in this first time in humans study, and induced similar immune responses to vaccination by IM injection.


Assuntos
Administração Cutânea , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Anticorpos Antivirais/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Voluntários Saudáveis , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/efeitos adversos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Placebos/administração & dosagem , Método Simples-Cego , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
8.
Cancer Res ; 63(18): 6032-41, 2003 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-14522932

RESUMO

This study assessed the immunological and clinical responses of women with human papillomavirus (HPV) 16-associated high-grade vulval intraepithelial neoplasia (VIN) vaccinated with TA-HPV, a recombinant vaccinia virus encoding modified HPV 16 and 18 E6 and E7. Eighteen women with HPV 16-positive high-grade VIN were vaccinated with TA-HPV. The extent of their baseline disease was compared after 24 weeks by lesion measurements and histological analysis. Viral load was assessed pre- and postvaccination by real time PCR. Cell-mediated immunity to HPV 16 E6 and/or E7 peptides (HLA-A2 epitopes) or vaccinia-infected cell lysates was determined by IFN-gamma enzyme-linked immunospot (ELISPOT) and T cell proliferation using an HPV 16 L2E6E7 fusion protein. Antibodies were measured by ELISA using vaccinia-infected cell lysates or HPV 16 and 18 E6 and E7 glutathione S-transferase-fusion proteins. Lesion-infiltrating CD4(+), CD8(+), CD1a(+), and CD68(+) immune cells were assessed by immunohistochemistry. The single vaccination with TA-HPV was well tolerated, and all patients showed an increased ELISPOT and/or antibody response to vaccinia. There were significant differences in HPV-16 E7-specific ELISPOT and L2E6E7 proliferative responses in the patients at one or more time points postvaccination as compared with the prevaccination status; two patients showed transient increased antibody responses. Overall, 13 women showed an increased HPV 16-specific immune response by one or more methodologies after immunization. Eight patients demonstrated a reduction in lesion diameter of at least 50% and a further four patients showed significant symptom relief. Viral load was reduced or cleared in six of eight lesion responders but also in six of ten nonresponders. Before vaccination, clinical responders had significantly higher levels of lesion-associated CD4(+), CD8(+), and CD1a(+)-immune cells than nonresponders. There were no differences in CD68 (macrophages) between responders and nonresponders before or after vaccination. Nonresponders did show a significant increase in CD4(+)- and CD8(+)- but not CD1a(+)-immune cells postvaccination but at lower levels overall than responder patients. Local immune infiltration may be a critical factor in potential responsiveness to vaccine therapy in HPV-associated neoplasia and should be carefully monitored in future placebo-controlled trials of immunotherapy for VIN.


Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma in Situ/imunologia , Carcinoma in Situ/terapia , Proteínas de Ligação a DNA , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/imunologia , Proteínas Repressoras , Vaccinia virus/genética , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/terapia , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Carcinoma in Situ/virologia , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Humanos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , Neoplasias Vulvares/virologia
10.
Clin Cancer Res ; 10(9): 2954-61, 2004 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15131030

RESUMO

PURPOSE: The purpose is to study the immunogenicity of heterologous prime-boost human papillomavirus (HPV) oncogene vaccination in patients with anogenital intraepithelial neoplasia (AGIN). EXPERIMENTAL DESIGN: Twenty-nine women with high-grade AGIN received three i.m. doses of TA-CIN (HPV-16 L2/E6/E7 protein) at four weekly intervals followed by a single dermal scarification of vaccinia HPV-16/18 E6/E7 and were followed up for 12 weeks. Immunity to HPV-16 was assessed by lymphoproliferation, IFN-gamma enzyme-linked immunospot (ELISPOT), and ELISA. RESULTS: The patient group significantly responded to TA-CIN and not to the control antigen HPV-6 L2/E7 at all postvaccination time points when compared with baseline responses (P < or = 0.05). Ten of the patients showed at least a 3-fold increase in TA-CIN-specific proliferation at one or more time points after vaccination. Comparison of stimulation with HPV-16 E6- or E7-GST fusion proteins showed that proliferative responses were biased to HPV-16 E6. This bias was also seen by IFN-gamma ELISPOT using overlapping peptides, with HPV-16 E6- or E7-specific T cells being detected in 9 and 2 patients, respectively. In addition, vaccination resulted in the induction of antibodies against the HPV-16 oncoproteins. Of the 6 clinical responders, 2 patients showed both a proliferative TA-CIN-specific response and an E6-specific IFN-gamma response, whereas 3 other patients displayed E6-specific reactivity only. Stable disease was recorded in 19 patients, 8 of whom showed a concomitant TA-CIN-specific proliferative and/or E6-specific T-cell response. Of the 4 progressors, 2 failed to make a T-cell response and 2 responded by either proliferation or E6 ELISPOT alone. CONCLUSIONS: The prime-boost regimen is immunogenic in AGIN patients (humoral and cellular immunity), but there is no simple relationship between induction of systemic HPV-16-specific immunity and clinical outcome. Other factors that may play a role in the eradication of long-term established AGIN lesions need to be determined to identify the patient group that would benefit from immunotherapy with the vaccines used in this study.


Assuntos
Neoplasias do Ânus/imunologia , Neoplasias dos Genitais Femininos/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Vacinas Virais/imunologia , Anticorpos Antivirais/sangue , Neoplasias do Ânus/prevenção & controle , Divisão Celular/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias dos Genitais Femininos/prevenção & controle , Humanos , Interferon gama/sangue , Proteínas Oncogênicas Virais/imunologia , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/prevenção & controle , Proteínas Repressoras/imunologia , Linfócitos T/imunologia , Fatores de Tempo , Vacinas Virais/administração & dosagem
11.
Clin Cancer Res ; 8(12): 3676-85, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12473576

RESUMO

PURPOSE: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs. We have conducted a study in patients with early-stage cervical cancer to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins. EXPERIMENTAL DESIGN: Twenty-nine patients with clinical International Federation of Gynecologists and Obstetricians (FIGO) stage Ib or IIa cervical cancer were given two vaccinations with TA-HPV at least 4 weeks apart, starting 2 weeks before radical hysterectomy. Patients were monitored closely for side effects of the vaccination. Serial blood samples were examined for HPV-specific CTLs or changes in levels of antibodies to HPV-16 or -18 E6 and E7 proteins and to vaccinia virus. RESULTS: Vaccination with recombinant vaccinia was well tolerated in all patients with only mild to moderate local toxicity, and no serious adverse events were attributable to the vaccine. After a single vaccination, HPV-specific CTLs were found in four patients (HLA A1, A3, three patients; HLA A1, A24, one patient). Eight patients developed HPV-specific serological responses. CONCLUSIONS: This study confirmed the safety and immunogenicity of the vaccine in a proportion of those patients vaccinated. Additional clinical studies using TA-HPV in combination with an additional experimental vaccine for HPV-16 are currently under way.


Assuntos
Proteínas de Ligação a DNA , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/uso terapêutico , Papillomaviridae/imunologia , Infecções por Papillomavirus/prevenção & controle , Proteínas Repressoras , Infecções Tumorais por Vírus/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adenocarcinoma/prevenção & controle , Adenocarcinoma/virologia , Adulto , Idoso , Anticorpos Antivirais/imunologia , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/virologia , DNA Viral/metabolismo , Feminino , Genótipo , Antígeno HLA-A1/metabolismo , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Estudos Soroepidemiológicos , Linfócitos T Citotóxicos/imunologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/virologia , Vacinação , Vacinas Sintéticas , Vaccinia virus/genética , Vacinas Virais/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologia
12.
Clin Cancer Res ; 9(14): 5205-13, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-14614000

RESUMO

PURPOSE: Anogenital intraepithelial neoplasia is a chronic disorder associated with infection by high-risk human papillomavirus (HPV) types. It is frequently multifocal and recurrence after conventional treatment is high. Boosting HPV-specific cell-mediated immune responses may reduce progression to carcinoma and could lead to disease clearance. We have tested the safety, immunogenicity, and efficacy of a recombinant vaccinia candidate vaccine (TA-HPV) in women with anogenital intraepithelial neoplasia. EXPERIMENTAL DESIGN: Twelve women, aged 42-54 years with high-grade HPV-positive vulval or vaginal intraepithelial neoplasia of up to 15 years duration, completed a Phase II study of TA-HPV, a live recombinant vaccinia virus, expressing modified versions of the E6 and E7 open reading frames from HPV-16 and HPV-18. RESULTS: The vaccine was well tolerated. Five of 12 (42%) patients showed at least a 50% reduction in total lesion diameter over 24 weeks with 1 patient showing complete regression of her lesion. Overall, 83% of women showed some improvement with an average decrease in lesion size of 40%. All cases showed an increased IgG titer and T-cell response to the vaccinia virus. An IFN-gamma enzyme-linked immunospot assay using pooled 22-mer peptides spanning HPV-16 E6 and E7 showed an increased specific T-cell response after vaccination in 6 of the 10 cases available for testing. There was no increase in specific cytotoxic response to selected individual HLA class I-restricted HPV-16 E6/7 peptides. CONCLUSIONS: The results suggest that the vaccine may have an effect on HPV-positive vulval intraepithelial neoplasia/vaginal intraepithelial neoplasia and that additional studies are warranted to develop an effective therapeutic vaccine.


Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma in Situ/terapia , Proteínas de Ligação a DNA , Papillomaviridae/genética , Infecções por Papillomavirus/terapia , Proteínas Repressoras , Vaccinia virus/genética , Neoplasias Vaginais/terapia , Neoplasias Vulvares/terapia , Adolescente , Adulto , Vacinas Anticâncer/efeitos adversos , Carcinoma in Situ/imunologia , Carcinoma in Situ/virologia , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Papillomaviridae/imunologia , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Segurança , Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Neoplasias Vaginais/imunologia , Neoplasias Vaginais/virologia , Neoplasias Vulvares/imunologia , Neoplasias Vulvares/virologia
13.
Vaccine ; 33(48): 6503-10, 2015 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-26478203

RESUMO

On 5-7 May 2014, the World Health Organization (WHO) convened the second integrated meeting on "influenza vaccines that induce broadly protective and long-lasting immune responses". Around 100 invited experts from academia, the vaccine industry, research and development funders, and regulatory and public health agencies attended the meeting. Areas covered included mechanisms of protection in natural influenza-virus infection and vaccine-induced immunity, new approaches to influenza-vaccine design and production, and novel routes of vaccine administration. A timely focus was on how this knowledge could be applied to both seasonal influenza and emerging viruses with pandemic potential such as influenza A (H7N9), currently circulating in China. Special attention was given to the development of possible universal influenza vaccines, given that the Global Vaccine Action Plan calls for at least one licensed universal influenza vaccine by 2020. This report highlights some of the topics discussed and provides an update on studies published since the report of the previous meeting.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Adjuvantes Imunológicos , Animais , Ensaios Clínicos como Assunto , Proteção Cruzada , Humanos , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/virologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Pandemias/prevenção & controle , Vacinação , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia , Organização Mundial da Saúde
14.
Recurso na Internet em Inglês | LIS - Localizador de Informação em Saúde | ID: lis-36895

RESUMO

Animação em Flash mostrando a infecção pelo vírus do Herpes Simples. Ilustra a contaminação, a infecção da pele, o movimentação do vírus dentro do corpo, seu estado de repouso e sua reativação. Documento SWF: requer o Macromedia Flash Player


Assuntos
Herpes Simples
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