Avaliaçao da resposta anticórpica a vacina recombinante anti-hepatite B, utilizando o GM-CSF como adjuvante vacinal em pacientes HIV positivos

Abstract

Resumo: Estudos sobre a imunogenicidade a vacina anti-hepatite B em pessoas infectadas pelo HIV tem mostrado respostas subotimas. Com o objetivo de melhorar a resposta anticorpica a vacina recombinante da hepatite B em pacientes HIV positivos, utilizou-se o rhGM-CSF(recombinant human granulocyte/macrophage colony-stimulating factor), que e uma citocina de acao imunoestimuladora e aumenta a resposta primaria de anticorpos. Estudos clinicos anteriores sugerem que o rhGM-CSF pode ser utilizado como um adjuvante-vacinai. Oitenta individuos com idade de 18 a 35 anos (media 28, anos), 40 homens e 40 mulheres portadores de HIV, com marcadores negativos para hepatite B, CD4/CD8 > 350 cels/mm3, foram incluidos em estudo duplo cego placebo/controlado. Os pacientes foram randomizados a receber uma dose de 20[xg do GM-CSF (Leucomax R) ou placebo intramuscular simultaneamente com 40 p.g de vacina recombinante antihepatite B (Engerix B R) no esquema 0, 1 e 6 meses. Os titulos de anti-HBs(>10mLU/ml) foram monitorados nos momentos 28, 60 e 210 dias apos a primeira dose da vacina; e a carga virai e os linfocitos CD4/CD8 nos momentos basal e 210 dias. As taxas de soroconversao apos a segunda dose da vacina foram de: 62%(25/40) para o grupo que usou o GM-CSF e 30%( 12/40 p<0,007) para o grupo controle. A media dos titulos protetores de anti-HBs avaliados nos 28 , 60 e 210 dias foram respectivamente de 40,3; 366,54 e 644,784 mLU/ml no grupo GM-CSF e de 62,4, 166,47 e 375,02 mlU/ml no grupo controle, com (p < 0,05) nos momentos 60 e 210 dias.O GM-CSF como adjuvante vacinai se mostrou seguro e eficaz, elevando os titulos de anti-HBs mais precocemente no grupo GM-CSF do que no grupo controle. A contagem de linfocitos CD4 e CD8 nao influenciou na soroconversao a vacina recombinante para hepatite B e a carga virai nao apresentou alteracoes significativas com o esquema vacinai. Nao se observou alteracao da imunogenicidade da vacina recombinante anti-hepatite B em relacao a idade, sexo e fator de risco.

Abstract: Recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGMCSF) is a cytokine with a potential vaccine adjuvant activity. It is also known that HIV infected patients often show poor immunologic responses to immunization. It was examined whether or not the use of locally applied GM-CSF could augment the immunologic response to recombinant vaccine against the hepatitis B virus (HBV) in patients infected with HIV. Eighty HIV-seropositive individuals, aged between 18 to 35 years old (mean age 28.02) ,42 male and 38 female, with CD4 lymphocyte count >350 cells/mm3 and negative markers for HBV, were included in a randomized, open-label study. All individuals received three doses of 40 jj.g of recombinant vaccine against HBV (EngerixR), administered at 0, 1 and 6 months. Concomitant with the first vaccine dose, 40 individuals received 20 jig of GM-CSF (Leucomax R) (the GM-CSF+HBVx group), and 40 individuals received placebo + HBVx (the control group). Seroconversion rates after the second dose ( day 60) were 25 (62%) for the GM-CSF+HBVx group and 12 (30%) for the control group (p<0.008). The average anti-HBs titers in patients with protecting levels (> 10 mUI/ml) after 28, 60 and 210 days were 40.3; 366.5 and 644.8 mUI/ml respectively in the GM-CSF group, and 62.4; 166.4 and 375.0 mUI/ml respectively in the control group. Significant differences were recorded at 60 and 210 days (p <0.01)). No significant differences were found between responders and nonresponders with regard to CD4 and CD8 lymphocytes counts, CD4/CD8 ratio, age, sex or risk group. No increase in the blood viral load RNA following vaccine administration was observed. No local or systemic adverse events were noted.This study suggests that 20 ug GM-CSF, used as a local vaccinal adjuvant, increases the immunogenicity of recombinant HBV vaccine, when it is administered to HIV infected individuals.