Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

Betancourt, Arístides Aguilar; Delgado, Concepción; Estévez, Zurina Cinza; Martínez, Julio; Ríos, Gloria Véliz; Aureoles-Roselló, S.R. Moreno; Zaldívar, Renzo A.; Guzman, Miguel; Baile, N. Figueroa; Reyes, Pedro A.; Ruano, L. Olivera; Fernández, Alex; Lobaina-Matos, Y.; Fernández, Audry; Madrazo, Alfonso; Martínez, Máximo; Baños, Manuel; Álvarez, Nadine; Baldo, M.; Mestre, R.E. Soto; Perez, Maira; Martinez, Micaela; Escobar, Daniel; Guanche, M.J. Cerna; Cáceres, Laura; Betancourt, Robert; Rando, Eugenio Hardy; Nieto, Gerardo Enrique Guillén; González, Verena Lucila Muzio; Rubido, Julio Cesar Aguilar

doi:10.1016/j.ijid.2006.09.010

Cited by 86 publications

(57 citation statements)

References 44 publications

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“…A novel immunization approach, based on the use of a combination of recombinant HBsAg and HBcAg (which both form virus-like particles), known as "NASVAC," is currently being developed for both the prevention and cure of hepatitis B (2). The vaccine was found to be safe and immunogenic, eliciting anti-HBc and anti-HBs seroconversion in a phase I/II trial (3,6).To our knowledge, PreS1 is the priority target antigen for the new HBV vaccines, because PreS1 has a greater number of immunogenic T cell and B cell epitopes than the S protein (9,12,15), including a strong T cell epitope (aa 21 to 28) and an effective B cell epitope (aa 12 to 32 and 32 to 53). The PreS1 protein has binding sites for liver cells (aa 21 to 47) that play an important role in viral attachment and entry (13,15).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Effect of DNA Immunization plus In Vivo Electroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids

Chen

Wen

Deng

et al. 2011

Clin Vaccine Immunol

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Hepatitis B virus (HBV) causes acute and chronic hepatitis and is associated with cirrhosis and liver cancer. Although the hepatitis B vaccine has been in use for over 20 years, HBV is still one of the most widespread pathogens (14). The most widely used HBV vaccine is a subunit vaccine containing the full-length S particle that is expressed by yeast or CHO cells (34). The HBV vaccine is very effective for mass immunization; however, 5% to 10% of the population do not produce protective anti-HBV surface (HBs) antigen antibodies, and in recent years, the S variant strains have increased in prevalence (5). The drugs that are currently used for the clinical treatment of hepatitis B include interferon and nucleoside analogues, such as lamivudine (5). Due to the limited effect of this drug treatment and the adverse reactions to their long-term application, new treatments for HBV, such as therapeutic HBV vaccines, are clearly needed (5).The direct injection of HBV DNA immunogens stimulates strong, long-lasting humoral and cellular immune responses in small-animal and chimpanzee models (11,18,22,25,27) and has become the focus of research on therapeutic HBV vaccines in recent years. However, applying these results to a larger population does not work well for small-animal models, and a large amount of DNA is needed to stimulate an effective immune response (17). Therefore, scientists are exploring ways to enhance the immunogenicity of DNA vaccines (1,16,30,32). Currently, electroporation is the most effective method for DNA vaccine delivery (16,30,32). Electroporation increases antigen (Ag) expression in muscle and skin 10-to 100-fold more than a direct injection, which leads to increased immunogenicity, a more durable response, and a reduced efficient dose in sheep, pigs, and other large animals.Another strategy for boosting the immunogenicity of DNA vaccines is to fuse exogenous B or T cell epitopes to virus-like particle (VLP) vectors to increase exposure after expression (26). After expression, a number of viral structural proteins automatically assemble into virus-like particles and can carry modified foreign epitopes without altering the particle's structure. For example, the widely used HBV and human papillomavirus (HPV) vaccines are virus-like particle immunogens. HBs antigen (29) and HBV core (HBc) antigen (10) were two of the first VLP antigens that were used to carry foreign epitopes (8,9,13,15,20,23,28,31,33).Previous data have shown that the HBCS1 that is expressed in Escherichia coli, containing core (amino acids [aa] 1 to 144) and PreS1 (aa 1 to 42), can form virus-like particles (33). Moreover, the HBSS1 that is expressed in CHO cells, containing S (aa 1 to 223) and PreS1 (aa 21 to 47), form stable, secreted virus-like particles with an equivalent molar ratio of PreS1 to S antigens (28). The two novel virus-like particle protein antigens can stimulate fast, effective humoral immune responses in animal models. Protein vaccines have a long life cycle and a complicated purification process and are expensiv...

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Section: Discussionmentioning

confidence: 99%

Enhanced Effect of DNA Immunization plus In Vivo Electroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids

Chen

Wen

Deng

et al. 2011

Clin Vaccine Immunol

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“…Only mild side effects was found, such as sneezing (34.1%), rhinorrhea (12.2%). 60 In the following phase IIa trial, 18 patients received 10 doses NASVAC containing 100mg HBsAg and 100mg HBcAg. Another 10 untreated CHB patients were enrolled into the study as control group.…”

Section: Hbsag Combines Antiviral Drugsmentioning

confidence: 99%

Research progress of therapeutic vaccines for treating chronic hepatitis B

Li¹,

Bao²,

Ge³

et al. 2017

Human Vaccines & Immunotherapeutics

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Hepatitis B virus (HBV) is a member of Hepadnavirus family, which leads to chronic infection in around 5% of patients with a high risk of developing liver cirrhosis, liver failure, and hepatocellular carcinoma. Despite the availability of prophylactic vaccines against hepatitis B for over 3 decades, there are still more than 2 billion people have been infected and 240 million of them were chronic. Antiviral therapies currently used in the treatment of CHB (chronic hepatitis B) infection include peg-interferon, standard a-interferon and nucleos/tide analogs (NAs), but none of them can provide sustained control of viral replication. As an alternative strategy, therapeutic vaccines for CHB patients have been widely studied and showed some promising efficacies in dozens of preclinical and clinical trials. In this article, we review current research progress in several types of therapeutic vaccines for CHB treatment, including proteinbased vaccines, DNA-based vaccines, live vector-based vaccines, peptide-based vaccines and cell-based therapies. These researches may provide some clues for developing new treatments in CHB infection.

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“…All volunteers gave Intranasal / subcutaneous simultaneous administration their written informed consent before enrollment, and the studies were conducted according to the principles set in the Declaration of Helsinki and in accordance with Good Clinical Practice requirements. First, the vaccine was evaluated in a phase I trial in healthy male adults [8]. In this initial trial all the adverse events reported were categorized as mild in intensity and self-limiting.…”

Section: Clinical Phase Of Developmentmentioning

confidence: 99%

“…The vaccine is based on a combination of the HBsAg and the HBV nucleocapsid (HBcAg) antigens and is simultaneously administered by the intranasal and subcutaneous routes [6,7]. ABX203 has been studied in phase I, phase II and phase III clinical trials with promising results [8][9][10]. In the present work we reviewed the results of the main preclinical and clinical trials of this product.…”

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confidence: 99%

ABX203, a novel therapeutic vaccine for chronic hepatitis B patients

2016

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Despite the existence of effective prophylactic vaccines, chronic hepatitis B remains a major public health problem, with more than 350 million people infected worldwide. Chronic infection increases the risk of serious liver diseases such as cirrhosis and hepatocellular carcinoma. Available therapies for chronic hepatitis B have limited efficacy and require long-term continuous treatments; that is why the development of therapeutic vaccines has been investigated as promising approach. In this sense, a novel vaccine formulation called ABX203 (HeberNasvac), based on the combination of the hepatitis B virus nucleocapsid and surface antigens, was developed. ABX203 has been studied in phase I, phase II and phase III clinical trial in treatment-naïve chronically infected patients in Bangladesh and in healthy volunteers in Cuba with promising results. In the present work we reviewed the main preclinical and clinical results of ABX203 development. Altogether, the data demonstrates safety and immunogenicity of ABX203 vaccine and support its use as a novel and competitive treatment alternative for chronic hepatitis B. The vaccine has been granted marketing authorization in Cuba.

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Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

Abstract: The HBsAg-HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens.

Cited by 86 publications

References 44 publications

Enhanced Effect of DNA Immunization plus In Vivo Electroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids

Enhanced Effect of DNA Immunization plus In Vivo Electroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids

Research progress of therapeutic vaccines for treating chronic hepatitis B

ABX203, a novel therapeutic vaccine for chronic hepatitis B patients

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