VACCINATION

Secondary immune reponse

Primary immune
response

Active immunity ACUTE PHASE

1. natural – illness
2. artificial - vaccines.
INCUBATION

Passive immunity
1. natural - transplacental and colostrum
transfer of Ab from mother to child.
2. artificial - Gamma Globulins.
VACCINATION- IMMUNOLOGIC MEMORY
VACCINE

PATHOGEN
 Smallpox eradicated in 1979 – Poxviridae family

1958- World Health Organization programme

to eradicate smallpox

(Edward Jenner, 1796)

Vaccinia -cowpox virus, cross antigenicity with
Smallpox virus
Macules- red spots; Papules-raised
bump; Vesicles-thick, opaque fluid,
depression in the center, Pustules-
sharply raised, belly-button, Crusts-
then scabs; Scars
 VIRAL VACCINES

1. LIVE ATTENUATED VACCINES- ”Attenuation” - weakening a virus

to the point where it can still provoke an immune response, but doesn’t cause illness in a
human host
• Cross reactivity between an animal virus -nonpathogenic for humans and a human virus
(vaccinia - smallpox)
• In vitro attenuation – “cold strains” (influenza, OPV anti polio Sabin, MMR, VZV, rotaviruses)
• Naturally attenuated strains (Max Theiler-yellow fever)

2. INACTIVATED VACCINES (influenza, IPV-anti polio Salk) viral

particles - grown in cell cultures / killed using heat, formaldehyde, etc

3. NEW VACCINE TECHNOLOGIES

 Immunization schedule ROMANIA 2020
AGE Vaccine Where

First 24 hours HepB Maternity ward

4-7 days BCG
2 months Hexavalent Vaccine (DTPa-IPV-Hib-Hep B) Family doctor
Pneumococcal conjugate vaccine *
4 months Hexavalent Vaccine (DTPa – IPV-HiB HepB) Family doctor
Pneumococcal conjugate vaccine *
11 months Hexavalent Vaccine (DTPa – IPV-Hib) Family doctor
Pneumococcal conjugate vaccine *
12 months MMR Family doctor
5 / 7 ys MMR Family doctor
6 ys / 8 ys Tetravalent Vaccine (DTPa-IPV) / IPV* Family doctor
14 ys DT adults/ DTPa Family doctor

Optional: 6-32 weaks - anti rotaviruses; 16-18 months anti-VZV, anti hepatitis A
Poliomyelitis (Picornaviridae) Bulbar Polio
Involvement of the medulla
- respiratory paralysis
Mortality rate
2–5% children
15–30% adults

asymptomatic infection
95% cases
abortive infection- 2-4%
- fever, fatigue, headache,
stiffness in the neck, pain in
the limbs

Spinal Polio- destroys the anterior horn cell

in the spinal cord

Accute flaccid paralysis – (AFP)- reduced muscle tone,

(limp), sudden onset, asymmetric, often permanent
neuronal damage
PicoRNAviridae RNAss+; naked
Poliovirus- 3 antigenic distinct serotypes (1,2,3)
Enterovirus- high environmental stability

Transmission- Faecal- oral route

Contaminated hands, water or food
Virus shed in oral secretions for several
weeks; feces for several months

Post-polio syndrome
•A prior episode of paralytic poliomyelitis with residual motor neuron loss (which can be confirmed
through a typical patient history, a neurologic examination, and, if needed, an electrodiagnostic
examination)
•A period of neurologic recovery followed by an interval (usually ≥15 years) of neurologic and
functional stability
•A gradual or abrupt onset of new weakness or abnormal muscle fatigue (decreased endurance),
muscle atrophy, or generalized fatigue
 VACCINES
SALK 1955 –IPV
INACTIVATED VACCINE
1952 US- 300,000 cases 58,000 deaths

Essential mutations in IRES 5’ NT

RNA secondary structure altered

Attenuated strains- “cold strains” suboptimal temperatures

SABIN 1962- OPV
LIVE ATTENUATED VACCINE
LIVE-ATTENUATED VACCINES- mimicking an asymptomatic
infection
ADVANTAGES
✓administration through natural routes (high
acceptability, low price)
✓global immune response (cellular, humoral,
local)
✓increased immunogenicity after first
administration, durable immunity
✓immune response against all native
antigenes (inactivation may alter the
antigenicity)
✓dissemination to contacts
DISADVANTAGES
➢Vaccine virus can revert to a form
capable of causing disease→VAPP
(VACCINE ASSOCIATED PARALYTIC
POLIO)
➢Severe reactions in
immunosuppressed persons
➢Maintenance of the cold chain
(during transport or storage)
➢Possible interference with viruses
that share the same habitat/ potential
contamination with animal viruses
infecting the isolation substrate (?)
VAPP –VACCINE ASSOCIATED PARALYTIC POLIO –1 in 2-3 millions doses
OPV strains can mutate during their replication in the human intestine and some mutations
may result in recovery of neurovirulence→ VDPV- vaccine derived polio virus

An excreted vaccine-virus can continue to circulate for an extended period of time in the
case of a low population immunity. The longer it is allowed to survive, the more genetic
changes it undergoes

polio type 2 accounts for about

40% of VAPP; in 2016- Switch
from trivalent OPV to → bivalent
OPV (only types 1 and 3 strains
of polio virus);

for 2020- Withdrawal of bivalent

OPV →use only IPV

2020
Afghanistan, Pakistan endemic
for wild type polio virus,

cVDPV- Burkina Faso, Niger,

Guinea
LIVE-ATTENUATED VACCINES- mimicking an asymptomatic infection

DISADVANTAGES
➢Vaccine virus can revert to a form
capable of causing disease→VAPP
(VACCINE ASSOCIATED PARALYTIC
POLIO)

➢Severe reactions in
immunosuppressed persons

➢Maintenance of the cold chain

(during transport or storage)

➢Possible interference with viruses

that share the same habitat/ potential
contamination with animal viruses
infecting the isolation substrate (?)
 Community
Immunity
("Herd” immunity)

When a critical
portion of a
community is
immunized against a
contagious disease,
most members of the
community are
protected against
that disease because
there is little
opportunity for an
outbreak.
 MMR-
trivalent live attenuated vaccine against:
• Measles
• Mumps
• Rubella
LIVE ATTENUATED VACCINES-
”Attenuation” - weakening a virus to the point
where it can still provoke an immune response,
but doesn’t cause illness in a human host
Measles virus – RNAss (-), enveloped
family: Paramixoviridae, genus: Morbilivirus
airborne virus, highly contagious

1. PNEUMOVIRUS:
*respiratory syncytial virus
(RSV)

2. MORBILIVIRUS:
*measles

3. PARAMIXOVIRUS:
*parainfluenza

4. RUBULAVIRUS:
*mumps

EXANTHEMA red-brown spotty rash
SYMPTOMS
- mild to severe fever, for several days
cold-like symptoms, such as
plus 3C – cough (+sneezing )
- coryza (runny nose ),
- conjunctivitis (watery eyes
and swollen eyelids)
ENANTHEMA- tiny greyish-white spots (called Koplik's
spots) in the mouth + throat
+/- tiredness irritability and general lack of energy,
aches and pains, poor appetite

Complications: Otitis; Pneumonia; Encephalytis/

SSPE-Subacute Sclerosing Panencephalitis
SSPE-Subacute Sclerosing Panencephalitis
• Rare, but fatal complication- M:F=2:1.
• in areas where measles vaccination is uncommon
• in those who acquire measles in the first 2 ys of life,
• Onset 7 to 20 years after infection with measles- most
cases occur in adolescence
• Defective viral strains- Mutants in F and M proteins - role
in assembly of virions
• Persistent measles infection in neurons, olygodendrocytes
• declining performance in school, behavioral changes,
headache, then mioclonic movements, and sometimes
seizures, ataxia, paralysis, spasticity, death
Positive diagnosis of SSPE:
1. an electroencephalographic pattern characteristic of SSPE
2. elevated levels of measles antibody (IgM) in cerebrospinal fluid
3. typical histopathologic changes in neurologic tissues derived at autopsy or from brain
biopsy specimens
4. identification of measles virus RNA by means of RT-PCR or measles antigen by
immunohistochemical analysis in brain tissues
 NO/INSUFFICIENT VACCINATION - RE-EMERGING VIRAL DISEASES
Recent epidemics of measles
EU - May 2011- April 2012- in EU; > 17 000 cases –
France, UK, Italy, Spain Romania- 83% / Germany, UK- 10%

Serbia - November 2014 - January 2015- 123 cases of measles

several outbreaks affecting numerous areas of the country.

Germany, Berlin- >400 cases; the outbreak started in October 2014 , initially
affected asylum seekers from Bosnia Herzegovina and Serbia, but has spread
to the general population; 28% of the cases needed hospitalisation; D8
genotype was identified

California, US - A large measles outbreak began after several people were

exposed to measles while visiting Disneyland between 17 and 20 December
2014; Patients range in age from seven months to 70 years; 25% of the
patients needed hospitalisation
Measles genotype –B3 -caused a large outbreak in the Philippines in 2014
Ohio, US – 2014-2015- unvaccinated Amish community - Measles genotype B3

Romania- 2016-2019- NW counties, -Communities with Suboptimal

vaccine coverage; Frequent travel outside and inside the country ;
imported B3 genotype
 OLD MYTHS

Vaccines DO NOT Cause Autism!!!

The MMR Hypothesis -1998 Lancet/research fraud by falsifying data about the children’s
conditions; 2010, Britain’s General Medical Council banned Wakefield from practicing medicine
in Britain
Anders Hviid, Jørgen Vinsløv Hansen, Morten Frisch, Mads Melbye. Measles, Mumps,
Rubella Vaccination and Autism. A Nationwide Cohort Study. Annals of Internal Medicine,
2019 - Nationwide cohort study in 657 461 children born in Denmark from 1999 - 2010
CONCLUSIONS:
The study strongly supports that MMR vaccination does not increase the risk for autism,
does not trigger autism in susceptible children, and is not associated with clustering of
autism cases after vaccination. It adds to previous studies through significant additional
statistical power and by addressing hypotheses of susceptible subgroups and clustering of
cases.
 MUMPS VIRUS - RNAss (-), fam. PARAMIXOVIRIDAE, genus
Rubulavirus

Merck Manual Consumer Version, ed. Robert Porter Copyright 2015

by Merck Sharp & Dohme Corp., merckmanuals.com. Complications:
•Meningitis, encephalitis
•Orchitis/ infertility
Swollen, painful salivary glands (parotitis) •Pancreatitis
Fever +/- Pain while chewing or swallowing
 RUBELLA
Rubella virus - RNAss+ enveloped - fam. Togaviridae, gen Rubivirus

Mean Incubation –17 days

Airborne transmission
Contagious: 7 days before/after rash

Complications:
A soft, pink rash on the face, quickly - Arthralgia or arthritis -70% of adults women
- Encephalitis
spreads to the trunk
Enlarged lymph nodes at the base of the skull/behind the ears
Rubella virus can be transmitted from mother to child, during
the First Trimester of pregnancy - congenital malformations

CONGENITAL RUBELLA SYNDROME

Sensorineural deafness

Eye abnormalities – retinopathy, cataract,

(a clouding of the lens in the eye leading
to a decrease in vision), microphthalmia

Congenital heart disease- pulmonary

artery stenosis; patent ductus arteriosus

ToRCH
 ROTAVIRUS- fam. REOVIRIDAE Severe DIARRHEA IN NEWBORNES
RNAds, segmented, naked AND INFANTS
Double capsid –epitopes involved in virus-neutralization
Viral enterotoxin – NSP4

Most common in infants and young children. Globally, it causes > half a million deaths each year in
children < 5 years of age.
Watery diarrhea, vomiting, fever, abdominal pain – 3-8 days +_dehydration
The virus spreads by the fecal-oral route (Hands /Objects /Food /Water)

Anti-rotaviral Vaccines - live attenuated

• Rotarix (GSK) –live attenuated, oral, human rotaviral strain; 2 doses po, every 4 weeks, until 24
weeks; first dose: 6 wks
• RotaTeq (MSD) – live attenuated, oral, pentavalent, reasortants between human- bovine
rotaviruses; po– 3 doses every 4 -10 weeks, until 36 weeks; first dose: 6 -12 wks
• Rare adverse events - intussusception- invagination
 New technology vaccines – Virus Like Particles (VLPs)
Generation of recombinant subunit vaccines

Exemples:
Anti hepatitis B vaccine

Anti HPV vaccine

Sintetic short peptides

insert the HBsAg gene into a yeast plasmid, which is transferred
into yeast cells.
Optimizing the antigenes presentation
Trial clinic faza II DNA, mRNA vaccines
Mderna Inc., Cambridge,
Mass) in colaborare cu
National Institute of Allergy
and Infectious Disease VIRAL VECTORS
(NIAID), SUA. VACCINES

COVID-19 vaccine-mRNA-
1273
ARNm sintetic care codifica
o forma stabilizata a
proteinei S
Delivery of the gene that encodes for the immune-dominant antigen

Advantages
a) induction of robust immune
responses, and increased cellular
immunity
b) highly specific delivery of genes
to target cells
c) trials are shortened by using the
vectorial platform
 VIRAL VECTORS VACCINES (EBOV, SARS CoV2)
Two viral platforms - harmless version of viruses

• Replication-competent virus :
Vesicular stomatitis virus (rVSV)

• Replication deficient virus:

Human recombinant adenovirus (rAd) or
Chimpanzee adenoviral vectors
mRNA vaccine technology
CDC
• https://www.cdc.gov/vaccines/index.html
• Advisory Committee on Immunization Practices (ACIP)-
• https://www.cdc.gov/vaccines/acip
• http://wwwnc.cdc.gov/travel/page/yellowbook-home

ECDC
• http://ecdc.europa.eu/en/healthtopics/immunisation/pag
es/index.aspx

WHO
• http://www.who.int/topics/immunization/en/

GAVI- GLOBAL VACCINE ALLIANCE http://www.gavi.org

• http://americanhistory.si.edu/polio/virusvaccine/index.ht
m
• http://www.astdhpphe.org/infect/polio.html- polio facts-
FAQ
• http://www.post-polio.org/