Area de Farmacologa

Facultad de Medicina
Universidad de Extremadura

Vacunas y Programas de Vacunaciones

SES
2015

Seguridad vacunal:
Precauciones y contraindicaciones de
las vacunas. Reacciones adversas.
Farmacovigilancia
Prof. Julio Bentez
Ctedra de Farmacologa
jbenitez@unex.es

Timelines for Vaccine Development

Major milestones and advances in vaccine development and the cumulative

number of licensed vaccines since the time of Edward Jenners first use of a
vaccination against smallpox in 1796.
GJ Nabel. N Engl J Med 2013;368:551-60

Timelines for Vaccine Development

Timeline for licensure of commercial vaccines against the indicated pathogens.

The abbreviation mAb denotes monoclonal antibody, OspA outer surface protein
A, rBS recombinant B subunit of cholera toxin, rDNA recombinant DNA, and WC
whole-cell Vibrio cholerae O1.
GJ Nabel. N Engl J Med 2013;368:551-60

Safety of Vaccines Used for Routine Immunization

of US Children: A Systematic Review
RESULTS: Of 20 478 titles identified, 67 were included. Strength of
evidence was high for measles/mumps/rubella (MMR) vaccine and
febrile seizures; the varicella vaccine was associated with complications
in immunodeficient individuals. There is strong evidence that MMR
vaccine is not associated with autism. There is moderate evidence
that rotavirus vaccines are associated with intussusception. Limitations
of the study include that the majority of studies did not investigate or
identify risk factors for AEs; and the severity of AEs was inconsistently
reported.

Maglione MA et al. PEDIATRICS Volume 134, Number 2, August 2014

Safety of Vaccines for Children (1)

Maglione MA et al. PEDIATRICS Volume 134, Number 2, August 2014

Safety of Vaccines for Children (2)

Maglione MA et al. PEDIATRICS Volume 134, Number 2, August 2014

Pre and postvaccine morbidity

Pre and postvaccine morbidity

Major global infections prevented by vaccines

Koff et al. Science 31 May 2013: 340 no 6136

Pre and post vaccines infectious diseases

GJ Nabel. N Engl J Med 2013;368:551-60

Infant mortality rate

The Principles and Practice of Medicine

William Osler, 1892
...si no fuera por
la gran variabilidad
entre los pacientes
la medicina podra
ser considerada
como una ciencia y
no un arte

DNA to Genome
1953 - 2001

Watson, DNA and Crick (1953)

Venter, Clinton & Collins (2001)

Vaccinomics
Vaccines licensed in the USA are safe and effective.
However, not every vaccine is equally safe or equally
effective in every person
Phenotype/genotype data, in combination with high
throughput genetic sequencing and bioinformatics, we
believe will accelerate the field of vaccinomics and

personalized vaccinology
For example, patients with renal failure or who are
immunocompromised may get a hepatitis B antigen dose
two- to four-times the usual dose in order to improve the
chances of seroconversion and protection.
Poland et al. Pharmacogenomics 2009, 10: 837-852

Vaccinomics
Genes involved in virus binding and cell entry,
antigen recognition, processing and presentation,
immune effector cell function and immunoregulation
are all necessary for a coordinated attack against an
invading pathogen
For these events to take place, a variety of genes
must be activated or suppressed and their products
transcribed and their proteins translated, modified,
expressed and secreted.

Interindividual variation to vaccination

Drug response
Therapeutic
level

Frequency

Toxic
level

Toxicity
Therapeutic
failure

Safety
&
Efficacy

Drug concentrations at steady state

Genetic polymorpisms
Therapeutic
level

Frequency

Toxic
level

Toxicity
Therapeutic
failure

Safety
&
Efficacy

Drug concentrations at steady state

Pharmacogenetics & pharmacogenomics publications

Pirmohamed M. Drug Discover today 16:852-861, 2011

Pharmacogenomics & Vaccinomics

The goal of pharmacogenomics and
vaccinomics is to identify genetic variants
that predict adverse responses to vaccines,
predict aberrant immune responses,
contribute to personalized therapy and that
predict susceptibility to diseases and
response to vaccines

Complement system polymorphisms

Most genes of the complement system are
polymorphic, with the C4 molecule having over
35 identified variants. While it has been
demonstrated that complement genes play a
critical role in the immune response to influenza ,
rubella and other viral infections, there have been
no studies to date investigating how complement
gene polymorphisms may affect immune response
to viral infections and/or viral vaccines.

Vaccinomics

The ability to respond to the threat of infectious disease

depends on the ability of the host to mount an effective
defense against an invading pathogen.

For this to occur, a variety of biologic systems must be

activated by the host, eventually resulting in the activation
and secretion of cytokines, antibodies, chemokines and
immune effector cells

Adversomics
Genetically determined vaccine-associated adverse
events have been called adversomics
Black et al. recognized differing and more severe
adverse events to receipt of the measles vaccine in
Amazon Basin Indians compared with other groups
suggesting a possible genetic contribution (J. Infect. Dis
1971;124:306317)

Twin vaccinomic studies

Some studies have observed a high heritability of 77%
for antibody response to hepatitis B vaccine in 207
Gambian twin pairs aged 5 months.
Heritabilities for antibody responses to oral polio,
tetanus and diphtheria vaccines were 60%, 44% and
49%, respectively.
In 100 twin pairs (45 MZ and 55 DZ) in Minnesota.
IgG levels heritability was 88% for measles, 39% for
mumps and 46% for rubella
Newport et al. Genes Immun 2004; 5:122129; Jacobson et al. Vaccine 2007; 25:31603164

Predictable, safe & efficient,

vaccine response ?
Yes we can