Lisset Hermida

• PhD
• Representative and PI at BCF and CCBJIC

The Hepatitis B core antigen (HBcAg) has been used as a carrier of several heterologous protein fragments based on its capacity to form virus-like particles (VLPs) and to activate innate and adaptive immune responses. In the present work, two chimeric proteins were designed as potential pancorona vaccine candidates, comprising the N- or C- terminal...

The Hepatitis B core antigen (HBcAg) has been used as a carrierof several heterologous protein fragments based on its capacity to form virus-like particles (VLPs)and to activate innate and adaptive immune responses. In the present work, two chimeric proteins were designed as potential pancorona vaccine candidates, comprising the N- or C- terminal d...

A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli. The N fragment belongs to the C-terminal domain whereas the S2 fragment spans the fibre structure in the post-fusion conformation of the spike protein. The resultant protein, nam...

Despite the rapid development of vaccines against COVID-19, they have important limitations, such as safety issues, the scope of their efficacy, and the induction of mucosal immunity. The present study proposes a potential component for a new generation of vaccines. The recombinant nucleocapsid (N) protein from the SARS-CoV-2 Delta variant was comb...

Several studies have reported the ability of the nucleocapsid (N) protein from the SARS-CoV-2 virus to interact with RNA in vitro. Nevertheless, its capacity to interact with deoxyribonucleic acid has yet to be widely described. In the present work, the nucleocapsid protein from the SARS-CoV-2 Delta variant was obtained in E. coli. The recombinant...

Due to the rapid development of new variants of SARS-CoV-2 as well as the real threat of new coronavirus zoonosis events, the development of a preventive vaccine with a broader scope of functionality is highly desirable. Previously, we reported the functionality of a nasal formulation containing the nucleocapsid protein and the receptor-binding dom...

Since the beginning of the pandemic, the pre-existing immunity against SARS-CoV-2 has been postulated as one possible cause of asymptomatic infections. Later, various works reported that pre-existing immune response against the two structural conserved antigens: S2 subunit and the nucleocapsid protein, were associated to some level of asymptomatic...

Despite the rapid development of vaccines and their reported efficacy for controlling the COVID-19 waves, two key challenges remain: the scope of the immunity against upcoming variants and zoonosis events, and the induction of mucosal immunity able to clear the virus in the upper respiratory tract for halting the transmission. The present study is...

Introducción: El dengue es una de las enfermedades más importantes trasmitida por mosquitos; sin embargo, solo existe una vacuna licenciada, la cual está registrada en 20 países. Sin embargo, la vacuna no podrá ser administrada en niños menores de nueve años de edad, dado el elevado riesgo de hospitalización observado en este grupo etario. Por lo t...

A novel coronavirus named SARS-CoV-2 is responsible for the present pneumonia outbreak called COVID-19 that started in early December 2019 in Wuhan City, Hubei province, China. Until March 12, SARS-CoV-2 had caused 80980 infections and 3173 deaths in China, but even worst, it is currently spreading fast in other countries, reaching 45293 infections...

Dengue is one of the most important diseases transmitted by mosquitoes. Dengvaxia®, a vaccine registered in several countries, cannot be administered to non-immune individuals and children younger than 9 years old, due to safety reasons. There are two vaccine candidates in phase 3 efficacy trials, but their registration date is completely unknown a...

The development of live-attenuated vaccines against Dengue virus (DENV) has been problematic. Dengvaxia, licensed in several countries where DENV is endemic, has shown low efficacy profiles and there are safety concerns prohibiting its administration to children younger than 9 years old, and the live-attenuated tetravalent vaccine (LATV) developed...

The development of an effective and safe vaccine against the Dengue virus has been limited by the absence of a definite correlate of protection, together with the possibility of amplification of the viral infection by the neutralizing antibody response of low affinity and concentration. However, the cellular immune response offers possibilities to...

Introduction: Dengue fever remains a health problem worldwide. Although the vaccine developed by Sanofi Pasteur, Dengvaxia®, has been registered in several countries, the results following the immunization of thousands of people suggest an increased risk in non-immune persons and children younger than 9 years old. No other vaccine is registered so...

Tetra DIIIC is a subunit vaccine candidate based on domain III of the envelope protein and the capsid protein of the four serotypes of dengue virus. This vaccine preparation contains the DIIIC proteins aggregated with a specific immunostimulatory oligodeoxynucleotide (ODN 39M). Tetra DIIIC has already been shown to be immunogenic and protective in...

Tetra DIIIC is a vaccine candidate against dengue virus (DENV) composed by four chimeric proteins that fuse the domain III of the envelope protein of each virus to the corresponding capsid protein. Containing B- and T-cell epitopes, these proteins form aggregates after the incubation with an immunostimulatory oligodeoxynucleotide, and their tetrava...

Our group has developed a subunit vaccine candidate against Dengue virus (DENV) based on two different viral regions, the domain III of the envelope protein and the capsid protein. The chimeric proteins for each serotype (DIIIC1-4), aggregated with the oligodeoxynucleotide 39 M, form the tetravalent formulation named Tetra DIIIC. Tetra DIIIC induce...

One of the major problems faced for the development of a vaccine against Dengue virus is the lack of a suitable animal model. Although non-human primates do not show overt signs of disease, these animals develop viremia after the infection and are the best model to evaluate vaccine candidates against this pathogen. However, for that purpose, the sc...

Una de las obras más completa publicada hasta ahora en idioma español. En ella se recopilan los conocimientos más avanzados acerca del agente causal, el vector, el hospedero y las alteraciones entre ellos, así como la clínica de la enfermedad, la epidemiología, la vigilancia y el diagnóstico de laboratorio, los métodos de prevención y control, el d...

Despite the considerable effort that has been invested in elucidating the mechanisms of protection and immunopathogenesis associated with dengue virus infections, a reliable correlate of protection against the disease remains to be found. Neutralizing Abs, long considered the prime component of a protective response, can exacerbate disease severity...

Most clinical isolates do not form clear plaques on cell monolayers. Therefore, they can not be detected by plaque assay. Reliable alternative methods for the measurement of viremia are thus required for the validation of the protective efficacy of dengue vaccine candidates against circulating virus strains. In this work, two different cell culture...

Transmission Electron Microscopy (TEM) is a valuable tool for the biotech industry. This paper summarizes some of the contributions of MET in the characterization of the recombinant antigens are part of vaccines or vaccine candidates obtained in the CIGB. It mentions the use of complementary techniques MET (Negative staining, and immunoelectron) th...

Despite the many efforts made by the scientific community in the development of vaccine candidates against dengue virus (DENV), no vaccine has been licensed up to date. Although the immunopathogenesis associated to the disease is a key factor to take into account by vaccine developers, the lack of animal models that reproduce the clinical signs of...

Bionatura • Volumen 1 / Número 2 • http://www.revistabionatura.com 71 71 Bionatura • Volumen 1 / Número 2 • http://www.revistabionatura.com 71 71 ABSTRACT Transmission Electron Microscopy (TEM) is a valuable tool for the biotech industry. This paper summarizes some of the contributions of MET in the characterization of the recombinant antigens are...

Dengue is an increasing public health problem worldwide, with the four serotypes of the virus infecting over 390 million people annually. There is no specific treatment or antiviral drug for dengue, and prevention is largely limited to controlling the mosquito vectors or disrupting the human-vector contact. Despite the considerable progress made in...

Background: Growth hormone secretagogues (GHS), among other factors, regulate the release of GH. The biological activity of the secretagogue peptide A233 as a promoter of growth and innate immunity in teleost fish has previously been demonstrated, but its role in the immune system of mammals is not well understood. Methods: The effect of the peptid...

There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full...

Vaccine formulations of the chimeric DIIIC-2 protein with different ODNs displaying adjuvant capacity were tested in mice against dengue virus serotype 2. DIIIC-2 comprises domain III from the envelope protein fused to the N-terminal region of the capsid protein. One of the ODNs, named ODN 39M, combines CpG motifs described as immunostimulatory act...

Our group developed a subunit vaccine candidate against dengue virus based on two different viral regions: the domain III of the envelope protein and the capsid protein. The novel chimeric protein from dengue-2 virus (domain III-capsid (DIIIC-2)), when presented as aggregated incorporating oligodeoxynucleotides, induced antiviral and neutralizing a...

Dengue disease is a global challenge for healthcare systems particularly during outbreaks, and millions of dollars are spent every year for vector control. An efficient and safe vaccine that is cost-effective could solve the burden that dengue virus imposes on affected countries. We describe here the immunogenicity of a tetravalent formulation of a...

Previously, we reported the ability of the chimeric protein DIIIC-2 (domain III of the dengue envelope protein fused to the capsid protein of dengue-2 virus), to induce immunity and protection in mice, when it is highly aggregated with a non-defined oligodeoxynucleotide (ODN) and adjuvanted in alum. In this work, three different defined ODNs were s...

Unlabelled: Dengue virus (DENV) infects an estimated 400 million people every year, causing prolonged morbidity and sometimes mortality. Development of an effective vaccine has been hampered by the lack of appropriate small animal models; mice are naturally not susceptible to DENV and only become infected if highly immunocompromised. Mouse models...

Recombinant fusion proteins containing domain III of the dengue virus envelope protein fused to the P64k protein from Neisseria meningitidis and domain III of dengue virus type 2 (D2) fused to the capsid protein of this serotype were immunogenic and conferred protection in mice against lethal challenge, as reported previously. Combining the domain...

The role of cellular immune response in dengue virus infection is not yet fully understood. Only few studies in murine models propose that CD8+ T-cells are associated with protection from infection and disease. At the light of recent reports about the protective role of CD8+ T-cells in humans and the no correlation between neutralizing antibodies a...

A dengue vaccine must induce protective immunity against the four serotypes of the virus. Our group has developed chimeric proteins consisting of the protein P64k from Neisseria meningitidis and the domain III from the four viral envelope proteins. In this study, the immunogenicity of a tetravalent vaccine formulation using aluminum hydroxide as ad...

Dengue is currently one of the most important arthropod-borne diseases, causing up to 25,000 deaths annually. There is currently no vaccine to prevent dengue virus infection, which needs a tetravalent vaccine approach. In this work, we describe the cloning and expression in Escherichia coli of envelope domain III-capsid chimeric proteins (DIIIC) of...

This study evaluated the use of a non-human primate, the olive baboon (Papio anubis), as a model of dengue infection. Olive baboons closely resemble humans genetically and physiologically and have been used extensively for assessing novel vaccine formulations. Two doses of dengue virus type 2 (DENV-2) were tested in baboons: 10(3) and 10(4) pfu. Si...

Live attenuated viruses are the most advanced candidates against a dengue infection. They have been demonstrated to be immunogenic in preclinical and clinical studies. However, due to their replicative capacity, they require several doses to achieve the balanced immune response against the four serotypes. The use of a suitable combination using non...

Live attenuated viruses are the most advanced candidates against a dengue infection. They have been demonstrated to be immunogenic in preclinical and clinical studies. However, due to their replicative capacity, they require several doses to achieve the balanced immune response against the four serotypes. The use of a suitable combination using non...

The existing vaccines are mainly limited to the microorganisms we are able to culture and produce and/or to those whose killing is mediated by humoral response (antibody mediated). It has been more difficult to develop vaccines capable of inducing a functional cellular response needed to prevent or cure chronic diseases. New strategies should be ta...

It was previously reported that DIIIC-2 (a fusion protein composed of domain III of the envelope protein and the capsid protein from dengue 2 virus), as an aggregate antigen from a partially purified preparation, induced a functional protective immune response against dengue 2 virus in the mouse encephalitis model. In the present work, a purificati...

In previous studies we reported the cloning, expression and purification of the capsid protein from Dengue-2 virus. Subsequently, we described an in vitro-assembly process for the capsid protein, which resulted in nucleocapsid-like particles (recNLPs) that induced functional cell-mediated immunity and protection in mice. Moreover, our group reporte...

The congress Biotecnología Habana 2012 was held at the Convention Center in Havana, Cuba, March 5-8. Organized by the Center for Genetic Engineering and Biotechnology (CIGB), this edition was dedicated to medical applications of biotechnology, with pre-Congress specialized satellite symposia and full conference sessions. Here we present information...

Recombinant fusion protein containing domain III of the dengue envelope protein fused to capsid protein from dengue 2 virus was immunogenic and conferred protection in mice against lethal challenge in previously report. Here, the antigenic specificity of this recombinant protein using anti-dengue antibodies from mice and humans and the cross-reacti...

The congress Biotecnología Habana 2012 was held at the Convention Center in Havana, Cuba, March 5-8. Organized by the Center for Genetic Engineering and Biotechnology (CIGB), this edition was dedicated to medical applications of biotechnology, with pre-Congress specialized satellite symposia and full conference sessions. Here we present information...

The interplay of different inflammatory cytokines induced during dengue virus infection plays a role in either protection or increased disease severity. In this sense, vaccine strategies incorporating whole virus are able to elicit both functional and pathological responses. Therefore, an ideal tetravalent vaccine candidate against dengue should be...

We previously tested in monkeys the P64k-DomIII fusion protein of DEN-2 (PD5), combined with the serogroup A capsular polysaccharide (CPS-A) from N. meningitidis as an immunopotentiator. The results revealed the induction of neutralizing antibodies and partial protection after DEN-2 challenge. Since one formulation of the CPS-A was only evaluated i...

Developing an effective vaccine entails: 1) proper antigenic presentation to the immune system, inducing a response of adequate intensity 2) a long duration for said response 3) the ability to steer this response towards the immune system pattern most suited for the elimination of the pathogen. Among the current crop of adjuvants, only aluminum-bas...

Developing an effective vaccine entails: 1) proper antigenic presentation to the immune system, inducing a response of adequate intensity 2) a long duration for said response 3) the ability to steer this response towards the immune system pattern most suited for the elimination of the pathogen. Among the current crop of adjuvants, only aluminum-bas...

Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time...

Here we evaluated the suitability of the synthetic adjuvant IC31® to potentiate the protective capacity of PD5 protein (domain III of the envelope protein of dengue 2 virus fused to the carrier protein P64k). Unlike Alum, PD5 mixed with IC31® induced complete protection against virus challenge in mice and increased IFN-γ secretion after in vitro re...

Existing vaccines are mainly limited to the microorganisms we are able to culture and produce and/or to those whose killing is mediated by humoral responses. It has been more difficult to develop vaccines capable to induce functional cellular responses needed to prevent or cure chronic diseases. Several results suggest that specific enhancement of...

In this study, we evaluate in mice a novel formulation containing nucleocapsid-like particles of dengue-2 virus (recNLP) co-immunized with a chimeric protein composed of the dengue-4 envelope domain III fused twice within the meningococcal P64k protein of Neisseria meningitidis (PD24). The animals receiving the PD24-recNLP mixture showed the highes...

A dengue vaccine should induce long-lasting, simultaneous protection to the four dengue viruses while avoiding the immune enhancement of viral infection. Domain III of the dengue envelope protein has been implicated in receptor binding, and is also the target of specific neutralizing antibodies. Domain III has emerged as a promising region for a su...

In this work we compared, in the same immunization schedule in mice, two vaccine candidates against Dengue-4 based on the envelope protein domain III and the carrier P64k. Their molecular and antigenic features, immunoge-nicity and protective capacity in the viral encephalitis murine model are assessed. Our study endorses the strategy of using both...

In the present work, we evaluated the neutralizing capacity of the antibodies induced by dengue virus type 1 and 2 envelope domain III recombinant proteins in monkeys against strains of different dengue virus type 1 and 2 genotypes. Here we demonstrated that dengue virus type 1 and 2 recombinant proteins induced high titers of neutralizing antibodi...

The aim of the present work was to test the concept of the heterologous prime-boost strategy combining an infective dengue virus with a recombinant chimeric protein carrying domain III of the envelope protein. Two studies in monkeys, combining recombinant protein PD5 (domain III of the envelope protein from dengue-2 virus, fused to the protein carr...

Based on the immunogenicity of domain III from the Envelope protein of dengue virus as well as the proven protective capacity of the capsid antigen, we have designed a novel domain III-capsid chimeric protein with the goal of obtaining a molecule potentially able to induce both humoral and cell-mediated immunity (CMI). After expression of the recom...

Testing in non-human primates is a generally accepted necessary step preceding the evaluation of dengue vaccine candidates in humans. A reduction of viremia in these animals after virus challenge is generally used as an indicator of vaccine efficacy. In this work, we compared the infectivity of three strains of dengue virus type 2 in a non-human pr...

New generation vaccines, particularly those based on recombinant proteins, are generally less reactogenic than traditional live attenuated vaccines. Nevertheless, in terms of immunogenicity, they require potent adjuvants to reach a proper immune response in the recipients. We had previously evaluated the potential capacity of PD5 protein (a vaccine...

New generation vaccines, particularly those based on recombinant proteins, are generally less reactogenic than traditional live attenuated vaccines. Nevertheless, in terms of immunogenicity, they require potent adjuvants to reach a proper immune response in the recipients. We had previously evaluated the potential capacity of PD5 protein (a vaccine...

The increasingly limited availability and high cost of the hitherto most commonly used monkey species in dengue vaccine research has augmented the importance of identifying alternative suitable models for these studies. In this study we examined the capacity of green monkeys (Chlorocebus aethiops sabaeus) to develop dengue viremia, and thus provide...

A vaccine against dengue virus must be able to induce an effective and equivalent immune response to the four viral serotypes; however, some studies have revealed that DEN4 (dengue-virus serotype 4) induces a weaker immune response than the others in quadrivalent (tetravalent') formulations. We have previously reported the protective capacity, in a...

For several years, researchers have known that the generation of neutralizing antibodies is a prerequisite for attaining adequate protection against dengue virus. Nevertheless, the cellular immune response is the principal arm of the adaptive immune system against non-cytopathic viruses such as dengue, as once the virus enters into the cell it is n...

The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope...

The capsid protein is one of the three structural proteins of flaviviruses and is the building block of the nucleocapsid. It has also a predominant role in the replication of dengue virus. To obtain nucleocapsid-like particles from recombinant dengue-2 capsid protein produced in E. coli, a purification process using cation exchange chromatography w...

Dengue viruses (DENVs) are human pathogens that constitute a significant threat worldwide. Since they up-regulate MHC class I molecules; the cell-mediated immunity may play an important role in the defense against viruses. In this work, we tested a CFSE-based assay in determining proliferative response of lymphocytes isolated from mice or monkeys p...

Here, the antigenic specificity of the recombinant fusion proteins containing aa 286-426 of the dengue envelope protein fused to P64k from Neisseria meningitidis and the cross-reactive antibody response induced in immunized mice and monkeys were evaluated. The anti-dengue mice antibodies showed a higher reactivity to the homologous recombinant prot...

Recombinant fusion proteins containing the aa 286-426 of the dengue envelope protein fused to P64k protein from Neisseria meningitidis have been previously reported. Particularly, the immunogenicity and protective capacity of the dengue 2 recombinant protein was demonstrated in Macaca fascicularis monkeys. Here we evaluate the recombinant fusion pr...

The suitability of dengue 2 envelope domain III recombinant fusion proteins [(fusion (PD5) and insertion (PD3) variants)] for inducing functional antibodies and a protective immune response in nonhuman primates has been reported. However, the evaluation of the antibody response after immunization did not correlate with the protection data as measur...

52 Nuevas evidencias acerca de la cápsida del virus como candidato vacunal contra el virus Dengue 2 sin la inducción de anticuerpos neutralizantes Introducción El dengue es la enfermedad viral transmitida por ar-trópodos más ampliamente difundida que afecta a la población humana. El agente causal de esta enferme-dad es el virus dengue (VD), pertene...

The invention relates to the pharmaceutical industry and describes a conserved area of the surface of the E protein, which can be used in the development of broad spectrum molecules which can be used in the prevention and/or treatment of infections caused by dengue virus 1-4 and other flaviviruses. The invention also relates to chimeric proteins wh...

In the present work, we study the immunogenicity and protective capacity of a recombinant capsid protein from Dengue-2 virus. The capsid gene was cloned under the T5 phage promoter and expressed in Escherichia coli. The recombinant protein was obtained mainly associated to the soluble fraction upon cellular disruption and exhibited a pattern of hig...

Among the Dengue virus structural proteins, the Envelope glycoprotein is the most important because of its antigenic characteristics. In this work, the E protein from Dengue-2 virus truncated at the C-terminus region was successfully expressed in Pichia pastoris. The E2trunc gene was cloned under the AOX1 promoter from P. pastoris and the signal pe...

The immunogenicity of the Envelope fragment from amino acid 284 to 426 of Dengue viruses, obtained as fusion proteins with P64k in Escherichia coli, has been previously tested by our group. Here, we studied two fusion proteins with P64k carrying the Envelope fragment from two strains of Dengue 3: H87 prototype strain (PD9) and an isolate from the N...

We have previously reported the construction and evaluation in mice of recombinant fusion proteins formed by a fragment (aa 286-426) of the dengue envelope protein and the P64k protein from Neisseria meningitidis. In this work we describe the immunization of Macaca fascicularis monkeys with two variants of these proteins [PD3 (insertion variant) an...

A fragment of the Envelope protein of Dengue 2 virus encoding the amino acid (aa) 286-426 was fused to the P64k protein from Neisseria meningitidis. The hybrid gene (PD5) was expressed in Escherichia coli. The influence of using immobilized metal ion affinity chromatography (IMAC) in the purification process of PD5 was examined. After the elution,...

Previously we have reported the capacity of the fusion protein PD3, composed of the P64k protein and the envelope (E) fragment from amino acids (aa) 286-426 of dengue-2 virus (DEN-2), to induce a functional immune response in mice against the homologous virus. In that case, the E fragment was inserted within the lipoyl-binding domain of the meningo...

A gene fragment encoding for the amino acids (aa) 286-426 from the dengue Envelope (E) protein was expressed in Escherichia coli as two forms of fusion proteins. In one case, the E fragment was fused to the first 45 aa of the P64k protein from Neisseria meningitidis (PD2) while, in the other, it was inserted within the lipoil-binding domain of the...

175 Potencialidad inmunogénica de la proteína de la envoltura del virus Dengue 4 expresada por vía recombinante en Pichia pastoris envoltura recombinante del virus Dengue 4 (E4rec) expresada en Pichia pastoris, mediante el estudio de la respuesta inmune inducida en ratones (BALB/c) y monos (Macaca fascicularis inmunizados fueron significativamente...

To characterize the effect of the envelope fragment fusion site in the P64k protein from Neisseria meningitidis several chimeric constructs were obtained. One variant consisted in the insertion of the E fragment from each Dengue serotype within the lipoil binding domain of the P64k, whereas the other was based on the fusion of the envelope fragment...

A recombinant vaccine that expresses the envelope (E) gene of dengue virus type 4 was tested for immunogenicity and protection in Macaca fascicularis. One hundred micrograms of semipurified recombinant E protein (E4rec) expressed in Pichia pastoris was used to immunize three animals. Neutralizing antibodies to dengue 4 virus with a titer of 1:30 we...