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Luana Moraes

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Papers by Luana Moraes

Research paper thumbnail of CRISPR/Cas9 Approach to Generate an Auxotrophic BCG Strain for Unmarked Expression of LTAK63 Adjuvant: A Tuberculosis Vaccine Candidate

Frontiers in Immunology

Tuberculosis is one of the deadliest infectious diseases and a huge healthcare burden in many cou... more Tuberculosis is one of the deadliest infectious diseases and a huge healthcare burden in many countries. New vaccines, including recombinant BCG-based candidates, are currently under evaluation in clinical trials. Our group previously showed that a recombinant BCG expressing LTAK63 (rBCG-LTAK63), a genetically detoxified subunit A of heat-labile toxin (LT) from Escherichia coli, induces improved protection against Mycobacterium tuberculosis (Mtb) in mouse models. This construct uses a traditional antibiotic resistance marker to enable heterologous expression. In order to avoid the use of these markers, not appropriate for human vaccines, we used CRISPR/Cas9 to generate unmarked mutations in the lysA gene, thus obtaining a lysine auxotrophic BCG strain. A mycobacterial vector carrying lysA and ltak63 gene was used to complement the auxotrophic BCG which co-expressed the LTAK63 antigen (rBCGΔ-LTAK63) at comparable levels to the original construct. The intranasal challenge with Mtb con...

Research paper thumbnail of SARS-CoV-2 vaccine development and how Brazil is contributing

Genetics and Molecular Biology, 2021

The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for... more The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for the development of vaccines. The most advanced strategies have focused on modifications of technologies that were already under development for other viruses, such as SARS, MERS, and even Influenza. Classic and new technologies, such as inactivated and attenuated viruses (non-replicative and replicative), DNA and mRNA vaccines, and nanoparticles containing SARS-CoV-2 antigens, are some of the strategies currently investigated. Although there is a very high expectation for the effectiveness of the most advanced vaccine candidates, there are still no established correlates of protection. Previous experience in vaccine development for other pathogens shows that differences in vaccine formulation can result in diverse immune responses and consequently, different protective properties. Therefore the importance of continuing investigations on a broad range of strategies. Expertise in vaccine development in Brazil was refocused to the new coronavirus. Impressive collaboration between institutions will support further developments until we have available a safe, effective, and economically viable vaccine. Established competence and collaborations will allow preparedness for future challenges and can also be used to address local issues as neglected infectious diseases.

Research paper thumbnail of Thirty years of recombinant BCG: new trends for a centenary vaccine

Expert Review of Vaccines, 2021

Research paper thumbnail of CRISPR/Cas9 Approach to Generate an Auxotrophic BCG Strain for Unmarked Expression of LTAK63 Adjuvant: A Tuberculosis Vaccine Candidate

Frontiers in Immunology

Tuberculosis is one of the deadliest infectious diseases and a huge healthcare burden in many cou... more Tuberculosis is one of the deadliest infectious diseases and a huge healthcare burden in many countries. New vaccines, including recombinant BCG-based candidates, are currently under evaluation in clinical trials. Our group previously showed that a recombinant BCG expressing LTAK63 (rBCG-LTAK63), a genetically detoxified subunit A of heat-labile toxin (LT) from Escherichia coli, induces improved protection against Mycobacterium tuberculosis (Mtb) in mouse models. This construct uses a traditional antibiotic resistance marker to enable heterologous expression. In order to avoid the use of these markers, not appropriate for human vaccines, we used CRISPR/Cas9 to generate unmarked mutations in the lysA gene, thus obtaining a lysine auxotrophic BCG strain. A mycobacterial vector carrying lysA and ltak63 gene was used to complement the auxotrophic BCG which co-expressed the LTAK63 antigen (rBCGΔ-LTAK63) at comparable levels to the original construct. The intranasal challenge with Mtb con...

Research paper thumbnail of SARS-CoV-2 vaccine development and how Brazil is contributing

Genetics and Molecular Biology, 2021

The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for... more The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for the development of vaccines. The most advanced strategies have focused on modifications of technologies that were already under development for other viruses, such as SARS, MERS, and even Influenza. Classic and new technologies, such as inactivated and attenuated viruses (non-replicative and replicative), DNA and mRNA vaccines, and nanoparticles containing SARS-CoV-2 antigens, are some of the strategies currently investigated. Although there is a very high expectation for the effectiveness of the most advanced vaccine candidates, there are still no established correlates of protection. Previous experience in vaccine development for other pathogens shows that differences in vaccine formulation can result in diverse immune responses and consequently, different protective properties. Therefore the importance of continuing investigations on a broad range of strategies. Expertise in vaccine development in Brazil was refocused to the new coronavirus. Impressive collaboration between institutions will support further developments until we have available a safe, effective, and economically viable vaccine. Established competence and collaborations will allow preparedness for future challenges and can also be used to address local issues as neglected infectious diseases.

Research paper thumbnail of Thirty years of recombinant BCG: new trends for a centenary vaccine

Expert Review of Vaccines, 2021

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