Advances of Reverse Vaccinology for mRNA Vaccine Design against SARS-CoV-2: A Review of Methods and Tools.

mRNA vaccines are a new class of vaccine that can induce potent and specific immune responses against various pathogens. However, the design of mRNA vaccines requires the identification and optimization of suitable antigens, which can be challenging and time consuming. Reverse vaccinology is a computational approach that can accelerate the discovery and development of mRNA vaccines by using genomic and proteomic data of the target pathogen. In this article, we review the advances of reverse vaccinology for mRNA vaccine design against SARS-CoV-2, the causative agent of COVID-19. We describe the steps of reverse vaccinology and compare the in silico tools used by different studies to design mRNA vaccines against SARS-CoV-2. We also discuss the challenges and limitations of reverse vaccinology and suggest future directions for its improvement. We conclude that reverse vaccinology is a promising and powerful approach to designing mRNA vaccines against SARS-CoV-2 and other emerging pathogens.

Computational vaccinology guided design of multi-epitope subunit vaccine against a neglected arbovirus of the Americas.

Mayaro virus (MAYV) is an arbovirus found in the Americas that can cause debilitating arthritogenic disease. Although it is an emerging virus, the only current approach is vector control, as there are no approved vaccines to prevent MAYV infection nor therapeutics to treat it. In search of an effective vaccine candidate against MAYV, we used immunoinformatics and molecular modeling to attempt to identify promiscuous T-cell epitopes of the nonstructural polyproteins (nsP1, nsP2, nsP3, and nsP4) from 127 MAYV genomes sequenced in the Americas (08 Bolivia, 72 Brazil, 04 French Guiana, 05 Haiti, 20 Peru, 04 Trinidad and Tobago, and 14 Venezuela). For this purpose, consensus sequences of 360 proteins were used to identify short protein sequences that can bind to MHC I class (MHC II). Our analysis revealed 56 potential MHC-I/TCD8+ (29 MHC-II/TCD4+) epitopes, but only 6 (16) TCD8+ (TCD4+) epitopes showed high antigenicity and conservation, non-allergenicity, non-toxicity, and excellent population coverage. Finally, classical and quantum mechanical calculations (QM:MM) were used to improve the quality of the docking calculations, with the QM part of the simulations performed using the density functional theory formalism (DFT). These results provide insights for the advancement of diagnostic platforms, vaccine development, and immunotherapeutic interventions.Communicated by Ramaswamy H. Sarma.

Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants.

The current COVID-19 pandemic, an infectious disease caused by the novel coronavirus (SARS-CoV-2), poses a threat to global health because of its high rate of spread and death. Currently, vaccination is the most effective method to prevent the spread of this disease. In the present study, we developed a novel multiepitope vaccine against SARS-CoV-2 containing Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (BA.1) variants. To this end, we performed a robust immunoinformatics approach based on multiple epitopes of the four structural proteins of SARS-CoV-2 (S, M, N, and E) from 475 SARS-CoV-2 genomes sequenced from the regions with the highest number of registered cases, namely the United States, India, Brazil, France, Germany, and the United Kingdom. To investigate the best immunogenic epitopes for linear B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL), we evaluated antigenicity, allergenicity, conservation, immunogenicity, toxicity, human population coverage, IFN-inducing, post-translational modifications, and physicochemical properties. The tertiary structure of a vaccine prototype was predicted, refined, and validated. Through docking experiments, we evaluated its molecular coupling to the key immune receptor Toll-Like Receptor 3 (TLR3). To improve the quality of docking calculations, quantum mechanics/molecular mechanics calculations (QM/MM) were used, with the QM part of the simulations performed using the density functional theory formalism (DFT). Cloning and codon optimization were performed for the successful expression of the vaccine in E. coli. Finally, we investigated the immunogenic properties and immune response of our SARS-CoV-2 multiepitope vaccine. The results of the simulations show that administering our prototype three times significantly increases the antibody response and decreases the amount of antigens. The proposed vaccine candidate should therefore be tested in clinical trials for its efficacy in neutralizing SARS-CoV-2.

Avanços sobre o Zika vírus pós-pandemia: uma revisão de literatura / Advances on the post-pandemic Zika virus: a literature review

Introdução: A infecção emergente pelo Zika vírus (ZIKV) tornou-se uma ameaça à saúde global devido à associação com anormalidades neurológicas graves: a síndrome de Guillain-Barré (SGB) em adultos e a síndrome congênita do Zika vírus (SCZ) em neonatos. O presente trabalho tem como intuito descrever os avanços sobre esta infecção relacionados aos aspectos epidemiológicos, clínicos, diagnóstico, prevenção e tratamento. Revisão da Literatura: Realizou-se uma revisão literária por meio de buscas bibliográficas nas bases de dados online LILACS, MEDLINE, Scopus e Web of Science, utilizando os descritores "Zika Virus", "Guillain-Barre Syndrome", "Zika Virus Infection", "Microcephaly", e "Congenital abnormalities", enfatizando os estudos realizados após o surto 2015- 2016 no Brasil. Discussão: O ZIKV já circulava no Brasil em 2013, um ano antes do que foi sugerido durante o surto. O teste molecular RT-PCR é o primeiro procedimento para a confirmação da doença, seguido pelo ensaio sorológico MACELISA. Embora a SCZ apresente achados neurológicos não patognomônicos nos fetos, exames radiológicos revelaram anormalidades mais comumente encontradas, destacando a microcefalia com padrão singular de "gaveta". Até o momento, não existem tratamentos antivirais e as vacinas não demonstram ser uma alternativa conveniente. Os alvos candidatos para o desenvolvimento destes medicamentos são as proteínas flavivirais NS1 e NS5, e a protease NS2B-NS3. Conclusão: Estes aspectos discutidos apontam a necessidade da criação de medicamentos antivirais e contribuem para o desenvolvimento de protocolos eficientes tanto no combate a novos surtos, como ao diagnóstico voltado a detecção do ZIKV e achados neurológicos da SCZ, possibilitando um tratamento mais eficaz ao paciente.

Introduction: The emerging Zika virus (ZIKV) infection has become a threat to global health due to the association with severe neurological abnormalities, being Guillain-Barré syndrome (GBS) in adults, and the congenital Zika virus syndrome (SCZ) in neonates. The present work aims to describe the advances in this infection, which refer to epidemiological, clinical, diagnosis, prevention, and treatment aspects. Literature Review: A literary review was carried out through bibliographic searches in the online databases LILACS, MEDLINE, Scopus, and Web of Science, using the descriptors "Zika Virus", "Guillain-Barre Syndrome", "Zika Virus Infection", "Microcephaly", and "Congenital abnormalities", emphasizing the studies carried out after the outbreak in Brazil (2015-2016). Discussion: The ZIKV was already circulating in Brazil in 2013, one year before what was suggested during the outbreak. The first procedure for confirming the disease is through the RT-PCR molecular test, followed by the MAC-ELISA serological test. Although SCZ presents non-pathognomonic neurological findings, radiological exams revealed abnormalities most found in fetuses with the syndrome, highlighting microcephaly due to the unique "drawer" pattern. There is no antiviral treatment, and vaccines have not proved to be a convenient alternative. Candidate targets for the development of these drugs are the flaviviral proteins NS1 and NS5, and the protease NS2B-NS3. Conclusion: These aspects discussed point to the need for the creation of antiviral drugs and contribute to the development of efficient protocols both to combat new outbreaks, as well as to the diagnosis aimed at the detection of ZIKV and neurological findings of SCZ, enabling a more effective treatment for the patient.