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1.
Open Forum Infect Dis ; 2(3): ofv082, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26199949

RESUMO

Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 10(3) to 3.4 × 10(7) particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results. Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions. An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases.

2.
J Infect Dis ; 192(12): 2129-33, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16288378

RESUMO

Pediatric AIDS Clinical Trials Group protocol 326 is a study of 2 formulations of recombinant canarypox ALVAC vaccine (vCP205) against human immunodeficiency virus type 1 (HIV-1). HIV-1-exposed infants were randomized to receive 1 of 2 formulations of vCP205 or placebo at birth and 4, 8, and 12 weeks. The vaccines were safe. Lymphoproliferative responses were detected at > or =2 time points in 44%-56% of vaccinees and none of the placebo recipients. A cytotoxic T lymphocyte response on at least 1 occasion was detected in 62.5% of infants in cohort 1 (10(6.08) median tissue culture dose [TCID(50)] vaccine formulation) and 44% of infants in cohort 2 (10(6.33) TCID(50) vaccine formulation). Rare mucosal immunoglobulin A responses and no measurable vaccine-elicited serum antibodies were detected. In children, vCP205 appeared to be safe and immunogenic.


Assuntos
Vacinas contra a AIDS/efeitos adversos , Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , Feminino , Anticorpos Anti-HIV/análise , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , Humanos , Imunoglobulina A Secretora/análise , Lactente , Recém-Nascido , Ativação Linfocitária , Mucosa/imunologia , Saliva/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia
3.
AIDS Res Hum Retroviruses ; 20(9): 916-26, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15597521

RESUMO

We performed a 24-week, placebo-controlled, comparative trial of hydroxyurea (HU) monotherapy, didanosine(ddI) monotherapy, and the combination of ddI plus HU administered as 1000 mg qd or 1500 mg qd in antiretroviral-naive and experienced subjects with CD4+ lymphocyte counts of 200-700 cells/mm3. Enrollment included 134 subjects. HU enhanced the antiviral activity of ddI by 1.0 log10 copies/ml after 8 weeks of therapy, with sustained responses over 24 weeks. HU alone over 4 weeks had no effect. Lamivudine resistance had little impact on antiretroviral activity when examined across treatment arms. Increases in absolute CD4+ T cell counts, but not CD4+ T cell percentages, were less in subjects who received HU compared to ddI monotherapy, and lymphoproliferative responses to antigenic and mitogenic stimuli were not altered. Subjects who received HU 1500 mg were more likely to experience dose-limiting hematological toxicities compared to those who received 1000 mg, without any additional antiviral benefit. HU may continue to have a role as a component of HIV therapy.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Hidroxiureia/uso terapêutico , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Didanosina/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Hidroxiureia/efeitos adversos , Masculino , Inibidores da Síntese de Ácido Nucleico/efeitos adversos , RNA Viral/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Resultado do Tratamento , Carga Viral
4.
Pediatrics ; 112(1 Pt 1): 66-73, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12837869

RESUMO

OBJECTIVE: Heptavalent pneumococcal conjugate vaccine (PCV) has been shown to be safe and effective in healthy infants and children. However, little is known about its use in children who have human immunodeficiency virus (HIV) infection and are known to be at increased risk of developing pneumococcal infections. This study was conducted to evaluate the safety and immunogenicity of heptavalent PCV in infants with HIV infection. METHODS: The Pediatric AIDS Clinical Trials Group Study 292 Team randomized infants with HIV infection 2:1 to receive heptavalent PCV or placebo in a double-blinded manner. Infants were vaccinated with 3 doses at 2-month intervals, starting at ages 56 to 180 days. A booster dose was given at 15 months of age. Immunogenicity was evaluated after the third dose of vaccine, before and after the booster dose, and at 24 months of age. RESULTS: Thirty infants with HIV infection received PCV, and 15 received placebo. No differences in baseline characteristics were found across arms. Five severe acute reactions were experienced by 4 subjects: 3 in the PCV arm and 1 in the placebo arm; all occurred among subjects with symptomatic disease at study entry. No differences were found in the 2 arms with respect to the number or timing of new diagnoses through 24 months of age, including diagnoses of otitis media. However, when symptomatic subjects were examined separately, the first new diagnosis occurred more rapidly among PCV recipients. Three deaths, all judged to be unrelated to study vaccine, occurred during follow-up: 2 in the PCV arm and 1 in the placebo arm. The primary immunogenicity measures were based on composites of 4-fold changes in serotype-specific immunoglobulin G titers from preimmunization levels. We found a highly significant difference between the vaccine and placebo arms, with the PCV arm showing higher rates of response. Asymptomatic and symptomatic subjects who received PCV had similar immunologic responses for all serotypes. CONCLUSIONS: This study demonstrates that heptavalent PCV was well tolerated and not associated with vaccine-associated adverse reactions. Most important, this vaccine was immunogenic in the infant with HIV infection. However, additional studies of this vaccine (or others) must pay special attention to patients with symptomatic HIV disease, as they seem to be at higher risk for adverse events to any antigen.


Assuntos
Infecções por HIV/imunologia , HIV-1 , Vacinas Meningocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Anticorpos Antibacterianos/biossíntese , Anticorpos Antibacterianos/sangue , Terapia Antirretroviral de Alta Atividade , Método Duplo-Cego , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Imunização Secundária , Imunocompetência , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Lactente , Masculino , Vacinas Meningocócicas/efeitos adversos , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/efeitos adversos , Risco , Segurança , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/imunologia , Vacinação
5.
J Infect Dis ; 187(2): 320-5, 2003 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-12552459

RESUMO

To ascertain whether CD4(+) lymphocyte increases induced by interleukin (IL)-2 enhanced in vivo immune responses, 38 human immunodeficiency virus (HIV)-infected patients who had received highly active antiretroviral therapy (HAART) or HAART and IL-2 for at least 60 weeks were immunized with tetanus toxoid, inactivated glycoprotein 120-depleted HIV-1, and hepatitis A and B vaccines. Despite dramatic increases in CD4(+) lymphocyte counts, IL-2 did not enhance immunization responses.


Assuntos
Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por HIV/imunologia , Interleucina-2/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Vacinas contra a AIDS/imunologia , Adjuvantes Imunológicos/farmacologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Vacinas contra Hepatite A/imunologia , Vacinas contra Hepatite B/imunologia , Humanos , Masculino , Toxoide Tetânico/imunologia
6.
AIDS Res Hum Retroviruses ; 18(9): 661-5, 2002 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-12079562

RESUMO

The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2). Plasma IL-6 and C-reactive protein (CRP) levels increased after rhIL-2 treatment. Etanercept pretreatment attenuated these increases. Median plasma IL-6 levels were 20.29 pg/ml 4 days after rhIL-2 and 7.87 pg/ml 4 days after etanercept and rhIL-2 (p = 0.22); median CRP levels were 78.73 and 46.16 microg/ml, respectively (p = 0.03). An effect on TNF bioactivity could not be assessed as all measurements were below limits of detection. No significant changes were seen in temperature or plasma levels of IL-4, IL-10, IL-12, interferon gamma, or HIV-1 RNA levels. All subjects had undetectable or low-level HIV-1 RNA levels before etanercept dosing. One subject died; however, her death was thought to be unrelated to etanercept. Pretreatment with etanercept may blunt activation of IL-6 and CRP expression induced by rhIL-2. The safety and utility of etanercept in HIV-infected persons should be explored further.


Assuntos
Infecções por HIV/metabolismo , Imunoglobulina G/farmacologia , Interleucina-2/antagonistas & inibidores , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/metabolismo , Terapia Antirretroviral de Alta Atividade , Proteína C-Reativa/metabolismo , Interações Medicamentosas , Etanercepte , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Fatores Imunológicos/farmacologia , Interleucina-2/uso terapêutico , Receptores do Fator de Necrose Tumoral , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/uso terapêutico
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