2021/10/04
Option 1
SARS-CoV 2 data set amount
1. The number of available Sars-CoV 2 genetic sequences
2. Use of the data for phylogenetic reconstruction. Focus on data quality
3. The input thinning importance (taxon-rich trees)
4. Conclusion
Option 2
MRCA role in determining vaccine candidates
1. SARS-CoV 2/RNA virus as challenge for vaccine development
2. The MRCA approach in vaccine candidates designing
4. Conclusion
Final
(after dicussing with the group)
MRCA role in determining vaccine candidates
1. MRCA concept
2. SARS-CoV 2/RNA virus as challenge for vaccine development
3. The MRCA approach in vaccine candidates designing
4. Conclusion
2021/10/05
After reading some papers during the afternoon:
Maybe do not focus only on MRCA. Instead, write about the role of phylogenetic reconstruction as a whole in designing vaccine candidates
After talking to Dan:
Classificação das variantes
Vigilância
Comparativo Influenza-Corona (tetra, trivalente; delta)
Outline
1. SARS-CoV2 background
a. Pandemic
b. RNA virus; high mutation rates
c. Spike protein; variants;
d. Resulting concern
Figure: variants; distribution in the country
2. Solving the problem
a. what is need to control?
b. vaccines; challenges
3. Talk about Influenza
a. Subtypes
b. Surveillance - phylogenetic reconstruction: its use on determining vaccine candidates
Figure: phylogenetic tree influenza subtypes with vaccines
c. Return to SARS-CoV2 variants - discuss
4. Conclusion
2021/10/06
After reading a little bit more about the currently scenario/studies
Outline
1. SARS-CoV-2 Background
a. Pandemic
b. spread
c. RNA virus; high mutation rates
d. problem to vaccine efficacy
Since its first notification in 2019, the RNA-stranded virus SARS-CoV-2 (Severe respiratory syndrome coronavirus 2) rapidly spread throughout the world population. The disease, Covid-19, a consequence of SARS-CoV-2 infection in humans, has resulted in millions of deaths worldwide. With unrestrained dispersion, the virus undergoes high mutations rates, which may affect the properties of the virus and potentially affect the performance of vaccines.
2. SARS-CoV-2 variants and influenza types, subtypes/lineages
a. Spike protein; variants
b. Describe influenza types, subtypes/lineages
c. Distribution of influenza types, subtypes/lineages
d. SARS-CoV-2 variants distribution
Figure: variants; distribution in the world
In SARS-CoV-2 genome, mutations on the structural spike protein originated the variants B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), B.1.1.28 (Gamma), B.1.232/B.1.427/B.1.429 (Epsilon), B.1.525 (Eta), B.1.526 (Iota), B.1.617.1 (Kappa), 1.617.3, B.1.621, B.1.621.1 (Mu), and P.2 (Zeta). Similarly, human seasonal influenza viruses, classified into types A and B, possess high mutations rates. Type A includes two subtypes, whilst type B, two lineages. Both can be further divided into different genetic clades and sub-clades. Importantly, the proportion of distribution of distinct influenza viruses can vary according to the geographic location. This same variated distribution profile occurs with SARS-CoV-2 variants.
3. Vaccines and phylogeny
a. Importance of investigating the distribution of the viruses
b. Influenza vaccines study
c. Phylogenetic inference will classify groups of interest
Figure: phylogenetic tree influenza subtypes with vaccine strains
4. Phylogenetic reconstruction
a. Surveillance - phylogenetic reconstruction
b. SARS-CoV2 variants – discuss
c. …
5. Conclusion
2021/10/07
Final version
The phylogenetic reconstruction as a support to design SARS-CoV-2 vaccine candidates
SARS-CoV-2 (Severe respiratory syndrome coronavirus 2) emerged in 2019 causing the coronavirus disease (COVID-19) in humans. With unrestrained dispersion, the virus spread worldwide (Andersen et al., 2020). SARS-CoV-2 possesses high mutations rates on its RNA-stranded genome, especially in the antigenic spike (S) protein, which have originated a series of variants (Jaroszewski et al., 2020; Lauring et al., 2021).
Studies report that random genetic drift in SARS-CoV-2 has played a central role in disseminating specific mutations across the world. Mutations on S protein, an epitope carrier, may affect the performance of vaccines, related to SARS-CoV-2 antigenic drift. As a consequence, despite vaccines administration, SARS-CoV-2 continues increasing the cases of COVID-19 (Yuan et al. 2019). Authors predict the permanence of this mechanism of variation in SARS-CoV-2 (Yuan et al., 2021), as with other RNA viruses, such as influenza and HIV (Karlsson et al., 2008). Because SARS-CoV-2 is likely to become endemic (Kissler et al., 2020), studies are in need to develop broadly effective vaccines (Yuan, et al. 2021; Dearlove, et al. 2020).
Predominant variants may diverge according to the region of circulation. Thus, a SARS-CoV-2 vaccine candidate should induce immune responses against circulating variants (Dearlove et al., 2020). Thus, an important tool for vaccine candidates design relies on the phylogenetic reconstruction. As a tool that groups consensus sequences, it infers possible matches between wild viral genetic sequences and vaccine candidates (Gaschen et al., 2002).
Influenza viruses are a useful example of phylogenetic reconstruction use to infer similarities between wild vaccine genetic sequences. With this approach, a study estimated the effectiveness of seasonal trivalent influenza vaccine (Fielding et al. 2016). Human seasonal influenza viruses are classified into types A and B. Type A includes two subtypes, whilst type B, two lineages. Both can be further divided into different genetic clades and sub-clades. All these antigenically differ from each other. Importantly, the proportion of distribution of distinct influenza viruses can vary according to the geographic location, thus, the study performed the phylogenetic reconstruction of the viruses obtained from patients from different Australian states. The phylogenetic tree presented clade mismatch between type A vaccine (A/Switzerland/9715293/13e), which previously presented findings of low efficacy, and circulating viruses (Figure 1).
Figure 1. Phylogenetic tree of haemagglutinin gene of selected influenza type A(H3) viruses forwarded to WHO Collaborating Centre for Reference and Research on Influenza (Melbourne), 2015. Viruses in blue were obtained from patients presenting influenza-like illnesses; those in red are vaccine reference viruses. The green arrow indicates the vaccine with low efficacy.
Source: Fielding et al., 2016. Adapted.
Similarly, a study applied the phylogenetic reconstruction in the developing of a SARS-CoV-2 vaccine candidates (Wang et al., 2020). These should cover the main SARS-CoV-2 populations from diverse geographical locations. Thus, SARS-CoV-2 was isolated from patients and three strains (CQ-01, QD-01, and HB-02) were obtained. These were applied on a phylogenetic reconstruction with 6,659 sequences. Sequences clustered into different groups based on sampling countries and the vaccine candidate scattering suggested coverage of the main circulating SARS-CoV-2 (Figure 2).
Figure 2. SARS-CoV-2 Maximum Likelihood Phylogenetic Tree. The SARS-CoV-2 isolates used in the study are indicated with black arrows and labeled. Viral strains (CQ-01, QD-01, and HB-02) were isolated from infected patients who traveled from the indicated continent/area.
Source: Wang et al., 2020.
Phylogenetic trees group consensus sequences and are useful in estimating similarities between wild viruses and vaccine candidates. Thus, phylogenetic reconstructions can provide supporting findings for the designing of SARS-CoV-2 vaccine candidates.
References
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Autoavaliação
Nota: 1.0
Justificativa: tudo o que aprendi a respeito de filogenia antes da disciplina foi sozinha. Portanto, quando iniciei, não tinha base dos fundamentos. Tudo ficou mais claro com as aulas. Aprendi bastante. Me dediquei o quanto pude. Somente conseguiria fazer mais (ler a literatura completa) se não tivesse conciliadas atividades presenciais no laboratório.
Estou muito satisfeita com meu desempenho.