Finally, the selection of candidates to pass on to experimental
evaluation will depend on knowledge (the more the better) on the
pathogen, its interaction with the host immune system and the
nature of the desired immune response(s), which in turn will
depend on the purpose of the vaccine (prophylactic or therapeutic).
Often, it is a good idea to rank the list of candidates according to
different sets of criteria, including apparently more mundane issues
such as everything around ease of production, solubility, stability,
and other properties of the proteins or peptides that might be
relevant to manufacturing and even dispensing the vaccine. The
prioritization of a given protein or set of proteins over others in the
initial in silico steps of reverse vaccinology remains challenging.
Even so, the reductionist nature of the approach results in a relatively manageable number of rationally selected potential vaccine
candidates amenable to experimental evaluation.
References
1. Levine MM, Dougan G, Good MF, Liu MA,
Nabel GJ, Nataro JP, Rappuoli R (2017) New
generation vaccines, 4th edn. Taylor & Francis Group, Boca Raton, FL
2. Bidmos FA, Siris S, Gladstone CA, Langford
PR (2018) Bacterial vaccine antigen discovery
in the reverse vaccinology 2.0 era: progress
and challenges. Front Immunol 9:2315.
https://doi.org/10.3389/fimmu.2018.
02315
3. Tettelin H, Masignani V, Cieslewicz MJ et al
(2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae:
implications for the microbial “pangenome.”. PNAS 102:13950–13955
4. Vernikos G, Medini D, Riley DR, Tettelin H
(2015) Ten years of pan-genome analyses.
Curr Opin Microbiol 23:148–154
5. Rappuoli R (2000) Reverse vaccinology. Curr
Opin Microbiol 3:445–450
6. Pizza M, Scarlato V, Masignani V et al (2000)
Identification of vaccine candidates against
serogroup B meningococcus by wholegenome sequencing. Science 287:1816–1820
7. Moriel DG, Scarselli M, Serino L, Mora M,
Rappuoli R, Masignani V (2008) Genomebased vaccine development: a short cut for
the future. Hum Vaccin 4:184–188
8. Moriel DG, Tan L, Goh KGK, Phan M-D, Ipe
DS, Lo AW, Peters KM, Ulett GC, Beatson
SA, Schembri MA (2016) A novel protective
vaccine antigen from the core Escherichia coli
genome. mSphere 1(6). https://doi.org/10.
1128/mSphere.00326-16
9. Moriel DG, Bertoldi I, Spagnuolo A et al
(2010) Identification of protective and
broadly conserved vaccine antigens from the
genome of extraintestinal pathogenic Escherichia coli. PNAS 107:9072–9077
10. Ariel N, Zvi A, Makarova KS, Chitlaru T,
Elhanany E, Velan B, Cohen S, Friedlander
AM, Shafferman A (2003) Genome-based
bioinformatic selection of chromosomal
Bacillus anthracis putative vaccine candidates
coupled with proteomic identification of
surface-associated antigens. Infect Immun
71:4563–4579
11. Amela I, Cedano J, Querol E (2007) Pathogen proteins eliciting antibodies do not share
epitopes with host proteins: a bioinformatics
approach. PLoS One 2:e512
12. Barh D, Tiwari S, Jain N, Ali A, Santos AR,
Misra AN, Azevedo V, Kumar A (2011) In
silico subtractive genomics for target identification in human bacterial pathogens. Drug
Dev Res 72:162–177
13. Rappuoli R, Pizza M, Masignani V, Vadivelu
K (2018) Meningococcal B vaccine
(4CMenB): the journey from research to real
world
experience.
Exp
Rev
Vaccin
17:1111–1121
14. Giuliani MM, Adu-Bobie J, Comanducci M
et al (2006) A universal vaccine for serogroup
B meningococcus. Proc Natl Acad Sci U S A
103:10834–10839
15. Tomar N, De RK (2014) Immunoinformatics: a brief review. Methods Mol Biol
1184:23–55
58
Daniel Yero et al.
evaluation will depend on knowledge (the more the better) on the
pathogen, its interaction with the host immune system and the
nature of the desired immune response(s), which in turn will
depend on the purpose of the vaccine (prophylactic or therapeutic).
Often, it is a good idea to rank the list of candidates according to
different sets of criteria, including apparently more mundane issues
such as everything around ease of production, solubility, stability,
and other properties of the proteins or peptides that might be
relevant to manufacturing and even dispensing the vaccine. The
prioritization of a given protein or set of proteins over others in the
initial in silico steps of reverse vaccinology remains challenging.
Even so, the reductionist nature of the approach results in a relatively manageable number of rationally selected potential vaccine
candidates amenable to experimental evaluation.
References
1. Levine MM, Dougan G, Good MF, Liu MA,
Nabel GJ, Nataro JP, Rappuoli R (2017) New
generation vaccines, 4th edn. Taylor & Francis Group, Boca Raton, FL
2. Bidmos FA, Siris S, Gladstone CA, Langford
PR (2018) Bacterial vaccine antigen discovery
in the reverse vaccinology 2.0 era: progress
and challenges. Front Immunol 9:2315.
https://doi.org/10.3389/fimmu.2018.
02315
3. Tettelin H, Masignani V, Cieslewicz MJ et al
(2005) Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae:
implications for the microbial “pangenome.”. PNAS 102:13950–13955
4. Vernikos G, Medini D, Riley DR, Tettelin H
(2015) Ten years of pan-genome analyses.
Curr Opin Microbiol 23:148–154
5. Rappuoli R (2000) Reverse vaccinology. Curr
Opin Microbiol 3:445–450
6. Pizza M, Scarlato V, Masignani V et al (2000)
Identification of vaccine candidates against
serogroup B meningococcus by wholegenome sequencing. Science 287:1816–1820
7. Moriel DG, Scarselli M, Serino L, Mora M,
Rappuoli R, Masignani V (2008) Genomebased vaccine development: a short cut for
the future. Hum Vaccin 4:184–188
8. Moriel DG, Tan L, Goh KGK, Phan M-D, Ipe
DS, Lo AW, Peters KM, Ulett GC, Beatson
SA, Schembri MA (2016) A novel protective
vaccine antigen from the core Escherichia coli
genome. mSphere 1(6). https://doi.org/10.
1128/mSphere.00326-16
9. Moriel DG, Bertoldi I, Spagnuolo A et al
(2010) Identification of protective and
broadly conserved vaccine antigens from the
genome of extraintestinal pathogenic Escherichia coli. PNAS 107:9072–9077
10. Ariel N, Zvi A, Makarova KS, Chitlaru T,
Elhanany E, Velan B, Cohen S, Friedlander
AM, Shafferman A (2003) Genome-based
bioinformatic selection of chromosomal
Bacillus anthracis putative vaccine candidates
coupled with proteomic identification of
surface-associated antigens. Infect Immun
71:4563–4579
11. Amela I, Cedano J, Querol E (2007) Pathogen proteins eliciting antibodies do not share
epitopes with host proteins: a bioinformatics
approach. PLoS One 2:e512
12. Barh D, Tiwari S, Jain N, Ali A, Santos AR,
Misra AN, Azevedo V, Kumar A (2011) In
silico subtractive genomics for target identification in human bacterial pathogens. Drug
Dev Res 72:162–177
13. Rappuoli R, Pizza M, Masignani V, Vadivelu
K (2018) Meningococcal B vaccine
(4CMenB): the journey from research to real
world
experience.
Exp
Rev
Vaccin
17:1111–1121
14. Giuliani MM, Adu-Bobie J, Comanducci M
et al (2006) A universal vaccine for serogroup
B meningococcus. Proc Natl Acad Sci U S A
103:10834–10839
15. Tomar N, De RK (2014) Immunoinformatics: a brief review. Methods Mol Biol
1184:23–55
58
Daniel Yero et al.