Publications by authors named "Laura Lazo"

Zika virus (ZIKV) infection remains a global public health problem. After the "Public Health Emergencies of International Concern" declared in February 2016, the incidence of new infections by this pathogen has been decreasing in many areas. However, there is still a likely risk that ZIKV will spread to more countries.

View Article and Find Full Text PDF
Article Synopsis
  • Despite the development of COVID-19 vaccines, there are concerns regarding their safety and effectiveness, particularly in inducing mucosal immunity.
  • The study investigates a new vaccine component by combining the nucleocapsid (N) protein from the Delta variant with a synthetic adjuvant, ODN-39M, and tests its effects in Balb/C mice.
  • Results show that intranasal administration of this combination generates a strong immune response, producing IgA in the lungs and neutralizing antibodies, making it a promising candidate for a more effective intranasal vaccine against various Sarbecoviruses.
View Article and Find Full Text PDF

Zika virus infection continues to be a global concern for human health due to the high-risk association of the disease with neurological disorders and microcephaly in newborn. Nowadays, no vaccine or specific antiviral treatment is available, and the development of safe and effective vaccines is yet a challenge. In this study, we obtained a novel subunit vaccine that combines two regions of zika genome, domain III of the envelope and the capsid, in a chimeric protein in E.

View Article and Find Full Text PDF

Since the beginning of the COVID-19 pandemic, the development of effective vaccines against this pathogen has been a priority for the scientific community. Several strategies have been developed including vaccines based on recombinant viral protein fragments. The receptor-binding domain (RBD) in the S1 subunit of S protein has been considered one of the main targets of neutralizing antibodies.

View Article and Find Full Text PDF

Umbilical cord blood (UCB) is a suitable source for hematopoietic stem cell transplantation. The study of HLA genes by next generation sequencing is commonly used in transplants. Donor/patient HLA matching is often higher within groups of common ancestry, however "Hispanic" is a broad category that fails to represent Argentina's complex genetic admixture.

View Article and Find Full Text PDF

Introduction: The induction of a functional immune response against the four viral serotypes is one of the premises for an effective vaccine against Dengue virus. This is challenging since the immunization with four antigens leads to immunologic phenomena such as antigen interference, immuno-dominance, and tolerance. Moreover, the four serotypes have intrinsic features that impact the outcome after the immunization with a tetravalent formulation.

View Article and Find Full Text PDF

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 at this moment.

View Article and Find Full Text PDF

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 by NIAID has proven too reactogenic during clinical trialing. In this work we examined whether the combination of TV005, a LATV-derived formulation, with Tetra DIIIC, a subunit vaccine candidate based on fusion proteins derived from structural proteins from all four DENV serotypes, can overcome the respective limitations of these two vaccine approaches.

View Article and Find Full Text PDF

Introduction: Dengue fever remains as a health problem worldwide. Although Dengvaxia®, was registered in several countries, the results after the immunization of people suggest an increase of risk in non-immune persons and children younger than 9 years old. No other vaccine is registered so far, thus the development of a safe and effective vaccine continues to be a priority for the WHO and the scientific community.

View Article and Find Full Text PDF

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 tetravalent formulation induces neutralizing antibodies and cellular immune response in mice and monkeys. Also, Tetra DIIIC protects mice after challenge with each DENV, and the monovalent formulation obtained from DENV-2 protects monkeys upon homologous viral challenge.

View Article and Find Full Text PDF

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 mice and monkeys.

View Article and Find Full Text PDF

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 when present at subprotective levels, and a growing body of data is challenging the notion that their titers are positively correlated with disease protection. Consequently, the protective role of cell-mediated immunity in the control of dengue infections has begun to be studied.

View Article and Find Full Text PDF

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 the disease has hampered the vaccine progress. Non-human primates support viral replication, but they are very expensive and do not show signs of disease.

View Article and Find Full Text PDF

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 protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate.

View Article and Find Full Text PDF

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 anti-viral and neutralizing antibodies, a cellular immune response and conferred significant protection to mice and monkeys. The remaining constructs were already obtained and properly characterized.

View Article and Find Full Text PDF

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 studied as aggregating agents. Our results suggest that the nature of the ODN influences the capacity of protein DIIIC-2 to activate cell-mediated immunity in mice.

View Article and Find Full Text PDF

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 and protection observed in several studies, a vaccine based on cell-mediated immunity constitute an attractive approach.

View Article and Find Full Text PDF

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 III-P64k recombinant proteins of dengue virus types 1, 3 and 4 (D1, D3, and D4) with the domain III-capsid protein from D2, we obtained a novel tetravalent formulation containing different antigens. Here, the IgG and neutralizing antibody response, the cellular immune response, and the protective capacity against lethal challenge in mice immunized with this tetravalent formulation were evaluated.

View Article and Find Full Text PDF

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 adjuvant was evaluated in mice.

View Article and Find Full Text PDF

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 the four dengue serotypes as a tetravalent dengue vaccine candidate that is potentially able to generate humoral and cellular immunity.

View Article and Find Full Text PDF

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 purification procedure was developed for DIIIC-2, and soluble and aggregated fractions of the purified protein were characterized and evaluated in mice. The purification process rendered a protein preparation of 91 % purity, and the remaining 9 % consisted of fragments and aggregates of the same recombinant protein.

View Article and Find Full Text PDF

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 reported the evaluation in non-human primates of the fusion protein P64k-domain III from Dengue-1 (PD10).

View Article and Find Full Text PDF

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 focused on serotype-specific sequences.

View Article and Find Full Text PDF