Freya Milagros Freyre, Jorge A Aguiar, Zurina Cinza, Nelvis Figueroa, Pablo Arsenio Diaz, Verena Lucila Muzio, Gilda Lemos, Giselle Freyre, Edelgis Coizeau, Chabeli Rodríguez, Eduardo Pentón, Magalys Campos, Iván Luis Santos, Mamun Al Mahtab, Sheikh Mohammad Fazle Akbar, Gerardo E Guillen, Julio Cesar Aguilar
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Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. The factorial analysis evidenced that the schedule combining the IN route of immunization and the frequency of 14 days resulted in the stronger antiviral and serological responses. Present results support the study of IN-only immunization schedules in future and was consistent with previous results. Long-lasting follow-ups were done to explore histological variables and the progression of serological variables in order to detect late responders.</p><p><strong>How to cite this article: </strong>Freyre FM, Aguiar JA, Cinza Z, <i>et al</i>. Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78.</p>","PeriodicalId":516317,"journal":{"name":"Euroasian journal of hepato-gastroenterology","volume":"13 2","pages":"73-78"},"PeriodicalIF":0.0000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10785140/pdf/","citationCount":"0","resultStr":"{\"title\":\"Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac.\",\"authors\":\"Freya Milagros Freyre, Jorge A Aguiar, Zurina Cinza, Nelvis Figueroa, Pablo Arsenio Diaz, Verena Lucila Muzio, Gilda Lemos, Giselle Freyre, Edelgis Coizeau, Chabeli Rodríguez, Eduardo Pentón, Magalys Campos, Iván Luis Santos, Mamun Al Mahtab, Sheikh Mohammad Fazle Akbar, Gerardo E Guillen, Julio Cesar Aguilar\",\"doi\":\"10.5005/jp-journals-10018-1402\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>HeberNasvac is a recently developed therapeutic vaccine for chronic hepatitis B (CHB) administered by intranasal (IN) and subcutaneous (SC) routes in a 14 days/10 doses schedule. To compare different schedules and routes of immunizations, a group of patients received four different vaccination regimens in a placebo-controlled factorial study. Subsequently, patients were followed for a minimum time of 48 weeks. Samples collected at the end of the follow-up were compared with initial samples. Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. 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引用次数: 0
摘要
HeberNasvac 是最近开发的一种治疗慢性乙型肝炎 (CHB) 的疫苗,通过鼻内 (IN) 和皮下 (SC) 途径接种,接种时间为 14 天/10 次。为了比较不同的免疫接种计划和途径,一组患者在安慰剂对照因子研究中接受了四种不同的疫苗接种方案。随后,对患者进行了至少 48 周的随访。将随访结束时采集的样本与初始样本进行比较。第一组和第二组分别每 14 天和 7 天通过 IN/SC 途径接种一次该产品。第三组和第四组仅通过 SC 途径接受治疗,治疗时间分别为 14 天和 7 天。一组 21 名慢性阻塞性肺病患者接受了四种不同方案的疫苗接种,8 名患者接受了安慰剂接种,共计 29 名患者。与基线水平相比,61.9%的疫苗接种者的 VL 下降了≥2Log,安慰剂组为 25%。47.6%的疫苗接种者的HBV水平降至检测不到,安慰剂组为25%。疫苗接种者中,9 人中有 4 人(44.4%)出现 HBeAg 消失和抗 HBeAg 血清转换,40%(20 人中有 8 人)出现抗 HBs 反应,安慰剂组无此反应。35.0%的疫苗接种者的 HBsAg 水平降低了≥1Log,而安慰剂治疗的患者中没有人出现这种情况。考虑到个体分析和因子分析,通过 IN/SC 途径免疫的 I 组和 II 组检测到 HBV DNA 显著降低。此外,与安慰剂组(25.0%)相比,通过 IN/SC 途径治疗的患者分组(G I + II)和每 14 天接种一次的患者分组(G I + III)中 VL 降至≥2Log 的患者比例也明显较高,分别为 72.7% 和 63.6%。与基线相比,每 14 天接种一次(G I + G III)的患者的 HBsAg 水平也有所下降。总之,在超过 48 周的无治疗随访后,HeberNasvac 治疗患者在抗病毒和血清学反应方面均优于安慰剂组。因子分析结果表明,结合 IN 免疫途径和 14 天免疫频次的方案可产生更强的抗病毒和血清学反应。目前的结果支持今后对纯 IN 免疫接种计划的研究,并与之前的结果一致。我们进行了长期随访,以探索组织学变量和血清学变量的进展,从而发现晚期应答者:Freyre FM, Aguiar JA, Cinza Z, et al.免疫途径和时间表对使用HeberNasvac治疗的慢性乙肝患者血清学和病毒学反应的影响。Euroasian J Hepato-Gastroenterol 2023;13(2):73-78.
Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac.
HeberNasvac is a recently developed therapeutic vaccine for chronic hepatitis B (CHB) administered by intranasal (IN) and subcutaneous (SC) routes in a 14 days/10 doses schedule. To compare different schedules and routes of immunizations, a group of patients received four different vaccination regimens in a placebo-controlled factorial study. Subsequently, patients were followed for a minimum time of 48 weeks. Samples collected at the end of the follow-up were compared with initial samples. Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. The factorial analysis evidenced that the schedule combining the IN route of immunization and the frequency of 14 days resulted in the stronger antiviral and serological responses. Present results support the study of IN-only immunization schedules in future and was consistent with previous results. Long-lasting follow-ups were done to explore histological variables and the progression of serological variables in order to detect late responders.
How to cite this article: Freyre FM, Aguiar JA, Cinza Z, et al. Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78.