Adverse reactions to vaccines for infectious diseases

Adverse Reactions to Vaccines
for Infectious Diseases
Suda Sibunruang, M.D.

Picture from www.med.umich.edu

Contents
• Overview of vaccine adverse events
• Type of reactions
• Potential allergens in vaccines
• Diagnosis and management

The ideal vaccine should be…
• Non- reactogenic
• Easy to administer
• Highly immunogenic
• Long-lasting immunity
No currently available vaccine meets
all of these criteria
Moylett E. and Hanson C. J Allergy Clin Immunol 2004;114:1010-20

Access from www.cdc.gov , 4 November 2014

Picture from http://sciencebasedpharmacy.files
Access 4 November, 2014

Kelso J. and Greenhawt M. Middleton’s Allergy 8th edition, 2013, 1384-1403

Evolution of an immunization program

Vaccine adverse events (AE)
• 20 vaccines are currently in use
• Billions of doses are administered worldwide
• Vaccine induced AE ranges between
3- 83 /100,000 doses according to
post-marketing surveillance data
Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

Moylett E. and Hanson C. J Allergy Clin Immunol 2004;114:1010-20

Allergic reactions to vaccines
• Range from 1/50,000 doses for DTP vaccine
to about 1 per 500,000 to 1,000,000 doses for
most other vaccines
Wood RA, Setse R, Halsey N. J Allergy Clin Immunol 2007;120:478-81

Report of vaccine ADR in 2012
688/ 55,747 = 1.23%
Spontaneous reports of adverse drug reaction 2012
ศูนย์เฝ้าระวังความปลอดภัยด้านผลิตภัณฑ์สุขภาพ สานักงานคณะกรรมการอาหารและยา
Access from http://thaihpvc.fda.moph.go.th 31 October 2014

Spontaneous reports of adverse drug reaction 2012
Example
ศูนย์เฝ้าระวังความปลอดภัยด้านผลิตภัณฑ์สุขภาพ สานักงานคณะกรรมการอาหารและยา
Access from http://thaihpvc.fda.moph.go.th 31 October 2014

Hypersensitivity reactions following
immunization
• Extent: local - systemic
• Timing: immediate - non-immediate
• Frequency: common - rare
• Severity: minor- moderate- major

Local reactions
• Most frequent adverse event
• Often falsely labeled as allergic
Caubet JC. and Ponvert C. Immunol Allergy Clin N Am 2014;34:597-613

Types of local reactions
• Mild local reactions
• Large local reactions/
Extensive limb swelling
• Subcutaneous nodules
• Local eczema
• Nevi associated with hypertrichosis

Mild local reactions
• Most frequent
• Non-specific inflammation
- Tissue damage by the puncture
- Injection of foreign material

Large local reactions
• Less common
• Varied vaccines, particularly those
containing toxoids and/or adjuvants

Large local reactions
Two patterns
1. Typical large local reactions
2. Extensive limb swelling

Typical Large local reactions
• Occur typically within 24–72 h
• Result of 2 mechanisms
- Antigen/adjuvant Toll Like Receptor
(TLR)-induced inflammation
- Arthus reaction

Residual antibodies still present in the host
due to previous sensitization
Picture from http://classconnection.s3.amazonaws.com

Rate of local reactions
• Higher after receiving multiple
doses of certain vaccines
• Shorter interval between the doses
was not associated with higher rates

Extensive limb swelling
• Less common but may be impressive
• Extend at least to the elbow or knee
• Arises within 24 h
• Looks like a benign reactive edema
• Probably results from extravasation
mechanisms
• Usually painless

Subcutaneous nodules
• Common in vaccines containing
aluminium salts (19% of patients)

Subcutaneous nodules
• Nonspecific inflammation
• Correlation between concentration of
aluminium hydroxide and frequency and size
of nodules
• Regress within a few weeks
• Patch tests are often negative
• Few cases of persistent nodules (most of
them had positive patch tests)

Local eczema
• Vaccines containing aluminium hydroxide,
thimerosal and formaldehyde
• Reported mainly in adults
• May extend beyond the injection area or
become generalized
• A non-immediate hypersensitivity has
been suggested by positive patch tests

Nevi associated with hypertrichosis
• Reported after BCG, tetanus, and
smallpox vaccination (rarely)
• The causal components responsible
for the reaction, as well as the exact
pathomechanisms remain unknown

Systemic reactions
• 5–13% of the patients being vaccinated
• Most frequent symptoms include fever,
rash, drowsiness and irritability
• Most result from non-specific
mechanisms

Systemic reactions
• Distinguish between immediate
reactions (IgE-mediated) and
non-immediate reactions
(non-IgE-mediated)
• Vasovagal attacks associated with
injections are common

Vanlandera A. and Hoppenbrouwers K. Vaccine 2014;32:3147–54

Number of students suffering adverse events following MMR
campaign in Australia, 1998 (n=651,615 students)
Adverse event
Faint/syncope
Syncopal fit
Anaphylaxis
Hyperventilation
Rash
Local allergic reaction
Severe immediate local reaction
Arthropathy
Fever
Anxiety
Lymphadenopathy
Number
17
13
4322
111
11
Source : Communicable Disease Intelligence (Australia), 29 October 1998

Method:
identified anaphylaxis between 1991-1997 from
automated databases and reviewed medical record
Result:
5 cases of vaccine-associated anaphylaxis
after 7,644,049 vaccine doses (0.65 cases/million doses)
Bohlke K. et al. J Allergy Clin Immunol 2004;113:536–42

Immediate reactions
• 1–3 reactions per million vaccine doses
• Amounts of patients reported reaction after
first vaccination suggests either a pre-sensitization
to a vaccine component or
non-immunologically mediated reaction
• Identification is important because risk of life
threatening anaphylaxis if re-exposure
Kelso J. et al. J Allergy Clin Immunol 2012;130:25–43
Fritsche P.,Helbling A.,Ballmer-Weber BK. Swiss Med Wkly 2010;140:238 – 46

Non-immediate reactions
• Common symptoms include MP rash, delayed
onset urticaria, and erythema multiforme
• Other immunologic reactions
(i.e. serum sickness, Henoch Schonlein
Purpura) are even rarer

Picture from www.biofarma.co.
Access 31 October 2014

Components of vaccines

Picture from www.vaccinesafety.edu

Vaccine components
• Microbial components
• Gelatin
• Egg & chicken protein
• Milk
• Yeast
• Latex
• Aluminium
• Thimerosal
• Antibiotics
• Dextran
• Rare allergic
components

Microbial components
• Anaphylactic reactions have been reported
• However, IgE-mediated reactions to vaccines
are more often caused by additive or residual
vaccine components

Gelatin
• Produced by partial hydrolysis of
collagen extracted from connective
tissues of animals, such as cows or pigs
• Contains potentially allergenic protein
• Bovine and porcine gelatins are
extensively cross-reactive
Kelso J. J Allergy Clin Immunol 2014;133:1509–18

Gelatin
• The incidence of gelatin allergy appears
to be higher in Japan, perhaps because
of an HLA type (DR 9) common in
Japanese

Gelatin-containing vaccines
• Influenza
(Fluzone, FluMist)
• Japanese
encephalitis
• MMR
• MMRV
• Rabies (RabAvert)
• Tick-borne
encephalitis
• Typhoid vaccine, live
oral
• Varicella
• Yellow fever
• Zoster

Ranging from 250 to 15,580 μg per dose
Kelso J. Ann Allergy Asthma Immunol 2013;110:397-401

Kelso J. et al. J Allergy Clin Immunol 1993;91:867-72

Objective: relation between systemic allergic reactions to
vaccines and the presence of anti-gelatin IgE
Patients: 26 children who had systemic immediate
reactions to vaccines-containing gelatin
Control: 26 children without allergic reactions to vaccines
Sakaguchi M., et al. J Allergy Clin Immunol 1996;98:1058-61

SakaguchiM., et al. J Allergy Clin Immunol 1996;98:1058-61

• Nine showed severe anaphylaxis
(Skin + airways +/- shock)
• Ten had mild anaphylaxis
(skin +/- airways + others)
• Seven had only urticaria

All the control children had no anti-gelatin IgE

7/26 had allergic
reactions on
ingestion of
gelatin-containing
foods

Conclusion:
1. Strong relationship between the systemic reactions
and anti-gelatin IgE in the sera
2. Questioning of vaccine recipients about allergy
associated with the ingestion of gelatin-containing
foods may help to prevent anaphylaxis
3. It appears that vaccination triggered the later
onset of food allergic reactions to gelatin

Recommendation
• Patients experienced anaphylaxis after
ingestion of gelatin should be evaluated prior
to receiving a gelatin-containing vaccine
• Symptomless consumption of gelatin does
not exclude an allergy to gelatin, as other
routes of sensitization have been
incriminated

Recommendation
• Patients sensitized to pork or beef are at
higher risk of reaction to gelatins, and
caution should be taken when administrating
gelatin-containing vaccines

Nakayama T. and Onoda K. Vaccine 200;25:570–6

Prick test to gelatin
• Dissolve 1 teaspoon (5 grams) of
sugared gelatin powder in 5 cc NSS

Ovalbumin-containing vaccines
• Influenza (IIV, LAIV)
• MMR
• Rabies (PCEC)
• Yellow fever

Picture from http://online.wsj.com

MMR & PCEC contain negligible of egg protein,
thus can be administered to recipients with egg allergy
in the usual manner

Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403.

Raw egg allergy
Kelso J. J Allergy Clin Immunol 2000;106:990

Raw egg allergy
• Vaccine is not heated at any time during
the manufacturing process
• Perhaps some of reactions are due to
unrecognized raw egg allergy
Kelso J. J Allergy Clin Immunol 2000;106:990

Rutkowski K. et.al. Int Arch Allergy Immunol 2013;161:274–8

Chicken proteins
• Can also be found in some vaccines (i.e.
yellow fever vaccine)
• May be responsible for reactions in chicken-allergic
recipients

Milk
• Casamino acids
• Casein
• Lactalbumin

Casamino acids/casein -containing
vaccines
• Growth media for these vaccines
contain casamino acids derived from
casein
• Nanograms quantities of casein are
present in the vaccines

Casamino acids-containing vaccines
• DTaP (Daptacel)
• DTaP-IPV/Hib (Pentacel)
• Td (Tenivac)
• Tdap (Adacel)
• Meningococcal (Menomune)
• Pneumococcal (PCV13 – Prevnar 13)

Casein-containing vaccines
• DTaP (Infanrix)
• DTaP + HepB + IPV (Pediarix)
• DTaP + IPV (Kinrix)
• Tdap (Boostrix)
• Typhoid (Vivotif)

lactalbumin-containing vaccines
• OPV

Background:
Tetanus toxin is produced by growing Clostridium tetani
in a modified Latham medium derived from bovine casein
or that the C. tetani is grown in modified Mueller-Miller
casamino acid medium
Method:
1. Reviewed 8 children with anaphylaxis to
booster doses of DTaP, DTP, or Tdap
2. Tested 8 lots of the vaccines for residual casein
Kattan JD, et al. J Allergy Clin Immunol 2011;128:215-8

Result:
• 6/8 of the patients had prior acute allergic
reactions to cow’s milk
• All had an increased milk-specific IgE level documented
within 2 years of the reaction to the vaccine

Conclusion:
Continuing the standard practice for DPT vaccination in
all children, but advise caution when administering
booster doses in highly sensitive milk-allergic children

Yeast
• Hepatitis B and human papillomavirus
(HPV) vaccines are manufactured using
recombinant strains of Saccharomyces
cerevisiae (common bakers’ yeast) and
contain residual yeast proteins

Yeast protein
• Hepatitis B vaccines - up to 25 mg/dose
• Quadrivalent HPV vaccine < 7 mg/dose

Period: 1990 – 2004
Method: passive surveillance
Result:
• 1991–2001,276 million doses of HBV were distributed
• 180,895 (all vaccines) AE reports to VAERS
• 107 patients had prior history of allergy to yeast
• 82/107 received HBV
• 15/107 had anaphylaxis (11 HBV+ 4 other vaccines)
DiMiceli L. et al. Vaccine 2006;24:703–7

Conclusion:
Recombinant yeast derived HBV pose minimal risk
of allergic reactions in yeast sensitive individuals

Yeast
• Skin tests with yeast-containing vaccines
should be carried out prior to administration
to patients with history of yeast allergy
• If positive, vaccine can still be administered,
but in graded doses

Latex
• Contains naturally occurring impurities
(e.g., plant proteins and peptides)
• Can be processed in 2 different ways
1. Natural rubber latex (NRL)
- Medical gloves, catheters
2. Dry natural rubber (DNR)
- Vial stoppers and tip of syringe plungers
Russell M., et al. Vaccine 2004;23:664–7

Latex
• Physical contact of the liquid vaccine
with the stopper can cause the release
of latex allergens into the solution
• Passing the needle throughout the
stopper and by retaining latex allergens
in or on the needle

Latex
Theoretical risk
• Administration of vaccines that have
been in contact with such packaging
could induce immediate-type allergic
reactions in latex allergic recipients

Period: 1991 – 2003
Method: Reviewed cases with prior allergy to latex and
developed immediate reactions
Result:
• 167,233 (all vaccines) AE reports to VAERS
• 147(0.1%) patients had prior history of allergy to latex
• 28/147 (19%) developed a possible allergic AE
• 14 cases reported a history of allergy to various drugs,
Russell M. et al. Vaccine 2004;23:664–7
foods or aeroallergens

Result (continue):
• 11 (39%) received influenza vaccines
• 4 (21%) received hepatitis B vaccines
• The remaining reported hepatitis A vaccine,MMR
tetanus and diphtheria toxoids, IPV, varicella vaccine,
anthrax vaccine adsorbed, and yellow fever vaccine

Conclusion:
• Minimal risk of immediate allergic reactions to
immunized latex-sensitive individuals using
vaccines that contain DNR in the packaging

“ If a person reports severe allergy to latex,
vaccines supplied in vials or syringes that contain
natural rubber latex should not be administered
unless the benefit of vaccination clearly outweighs
the risk for a potential allergic reaction.
In these cases, providers should be prepared to
treat patients who are having an allergic reaction.
For latex allergies other than anaphylaxis,
vaccines supplied in vials or syringes that contain
dry, natural rubber or natural rubber latex
may be administered ”
General recommendations on immunization:
recommendations of ACIP. MMWR 2011;60:RR1-64

Latex
• Avoid passing the needle through the
stopper
• Stopper should be removed and the
vaccine drawn up directly from the vial

Latex
• Vaccine vial stoppers and syringe
plungers are made of synthetic rubber
and pose no risk to latex-allergic
persons

www.cdc.gov/vaccines/pubs/pinkbook/pink-appendx.htm

Aluminium
• Persistent itching, subcutaneous nodules, or
granulomas at the injection site
• Hyper- and hypopigmentation,
hypertrichosis, and lichenification have been
associated with such nodules
• In rare cases, nodules become inflammatory
and turn into an aseptic abscess
• Transient but can sometimes persist for a few
weeks or even years

Aluminium
• In aluminium-sensitized patients requiring a
vaccine containing aluminium, the injection
should be administered deep enough as
intramuscular administration may prevent
the formation of granulomas

Thimerosal
• One of the most effective preservative,
improving vaccine stability, potency, and
safety
• However, it has been less used over the last
decades in childhood vaccines, as a
precautionary measure due to its mercury
content

Thimerosal
• Not definitely caused immediate reactions
• Non-immediate reactions
(contact dermatitis and generalized MP rash)

Thimerosal
• If possible, alternative vaccines not
containing this preservative should be chosen
• The vast majority of patients with proven
sensitization to thimerosal as demonstrated
by positive patch tests tolerate thimerosal-containing
vaccines

Antibiotic containing vaccines

Antibiotics
• Some vaccines (i.e. polio, MMR, and
influenza vaccines) may contain traces of
antibiotics used for viral culture to avoid
bacterial and fungal contamination during
the manufacturing process

Antibiotics
• Although antibiotics in vaccines theoretically
could cause anaphylactic reactions, there is
no report of confirmed immediate reactions
• Nevertheless, the few patients who have a
confirmed immediate allergy to one of these
antibiotics should not receive vaccines
containing them

Neomycin containing vaccines in Switzerland

Neomycin
• Only single report of anaphylaxis
• Topical neomycin is known to elicit contact
dermatitis (delay-type reactions: DTR)
• However, amount of neomycin found in
vaccines is not believed to trigger DTR
• Thus, these vaccines may be given to
patients with DTR to neomycin

Other antibiotics
• Streptomycin, gentamycin, polymyxin B
sulphate and chlortetracycline have
been reported to trigger allergic
reactions in clinical use
• But… in term of vaccination they have
not yet been identified as a causative
agent of severe allergic reactions

Dextran
• Immediate reactions to BCG, and to some
MMR vaccines
• MMR containing dextran have now been
withdrawn from the market
• Now, may present in some rotavirus vaccines
• Non-immediate reactions to dextran are rare

Rare allergenic components
• Polysorbate (Tween), polygelines,
amphotericin B, protamine sulphate and
phenol red
• No evidence for hypersensitivity
reactions of these substances linked to
vaccination

Diagnosis & Management
“ Accurate diagnosis of vaccine allergy is
important not only to prevent serious or
even life-threatening reactions, but also
to avoid unnecessary vaccine restriction ”
Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403.

Two circumstances bring patients to allergists
1. Experienced adverse events
following immunization
2. Possible allergy to some
vaccine component, but have
never received the vaccine

1. Experienced adverse events
following immunization
Patient received an immunization experienced an adverse event
• Immunization may or may not have caused AE
• If causal,
the mechanism may or may not have been immunologic
• If immunologic,
the mechanism may or may not have been IgE mediated

Whether such patients can receive
additional doses of the suspect vaccine ?
Determine nature of AE - IgE mediated ?
Testing for IgE to the vaccine and
vaccine components

Determination of culprit allergen is important
because the same ingredient may be
found in other vaccines

2. Possible allergy to some vaccine components,
but have never received the vaccine
Whether such patients can receive vaccines
that contain these components ?
Determine nature of
reaction - IgE mediated ?
Testing for IgE to suspect allergen

Even patients have specific IgE to
a vaccine and/or vaccine component,
it is still likely that they can be immunized
with appropriate precautions

+/- IgE
Caubet JC. and Ponvert C. Immunol Allergy Clin N Am 2014;34:597–613

Start with a detailed history
Wood R., et al. Pediatrics 2008;122:e771–7

Management of local reactions (1)
• Mostly, local reactions subside
spontaneously without sequelae
• No association with a higher rate of
systemic reactions on re-exposure

Management of local reactions (2)
• Usually, no allergy test is required
• Serum vaccine-specific antibodies (IgM
or IgG) are indicated in patients with
suspicion of Arthus reaction

Patch test
• Demonstrate a delayed hypersensitivity to
preservatives or adjuvants
• They are not accurate for the purpose of
assessing a patient’s ability to tolerate a
vaccine
• Positive patch test may guide clinicians to
administer a vaccine free of these
components, if available

Prevention of local reactions (1)
• Correct needle length
Longer needle - -> lower rate of local reactions
• Site of injection
Injection in the thigh in children < 3 years
• Receive a vaccine free of the sensitized
component, if available

Prevention of local reactions (2)
• In patients reporting important local
inflammatory reactions after injection
of combined vaccines, sequential
injections of single or limited numbers
of vaccinating agents, every few days,
preferably intramuscularly, are usually
well tolerated

Immediate reaction
• Allergologic work-up should be carried out
even if no further doses of the suspected
vaccine are required
• Potential for cross-reaction with common
components in other vaccines and foods

Method: patients diagnosed of vaccine-induced
anaphylaxis were subjected to standardized allergy testing
Objective:
1. identify vaccination-associated IgE-mediated
Seitz C. et al. Vaccine 2009;27:3885–9
anaphylaxis
2. proofed reliability of reporting vaccine-induced
allergic anaphylaxis by HCW

Skin & SC
Respiratory or CVS or GI
Hypoxia, hypotension, neuro

undiluted vaccine for prick test
with positive-negative control
tetanus-/diphtheria-toxoid (17×),
hepatitis A/B (8×),TBE (7×),
influenza (6×)
10%;30%;60%
1 hr interval
without history of
allergy to egg, yeast, ATB

Conclusion:
• History of anaphylaxis after vaccination may not be
absolute contraindication for re-vaccination
• All anaphylaxis in fact not induced by an
IgE-mediated vaccine allergy

Wood R., et al. Pediatrics 2008;122:e771–7

Skin test
• Should be performed with the same brand
Prick method with undiluted vaccine
If negative
Intradermal skin test with
0.02 cc of vaccine diluted 1:100

Skin test
• If the initial vaccine reaction was life
threatening, it is appropriate to use diluted
vaccine for the skin prick test

Diagnostic course of SPT with vaccines

Skin test
• If positive skin test result, the same vaccine
skin test should be conducted in several
control subjects who have received vaccine
without adverse reaction

Skin test
• Sensitivity and specificity are not optimal,
but the main purpose of these tests is to
identify patients who are at real risk of
developing a severe anaphylactic reaction
in case of re-exposure

Skin test
• Intradermal skin tests with some
vaccines, such as tetanus toxoid, can
also induce delayed-type
hypersensitivity responses

Caubet JC. and Ponvert C. Immunol Allergy Clin N Am 2014;34:597–613
+/- IgE
Observe 30 min afterward

Negative skin test
• If the patient has a history strongly
suggestive of a severe anaphylactic reaction
• Some authors still recommend to administer
the vaccine in 2 doses
(10% followed 30 min later by
the remaining 90%)

Vaccine administration
• Administration of a vaccine should be
performed in a secure environment
(trained personnel onsite and
emergency drugs available)

Patient’s immune status to the vaccine
Risk Benefit

Immune status to the vaccine
• Measurement of antibodies to the
immunizing agent in a vaccine
• If a patient has already maintains protective
levels of antibody, withholding or delaying
subsequent doses may be appropriate

Micheletti F. et al. Clinical & Experimental Allergy 2012;42:1088-96

“ Egg allergy of any severity
(including anaphylaxis) is not a contraindication
to the administration of influenza vaccine
but rather a precaution ”

• Skin testing before
administration is not
recommended because
of its low sensitivity
and specificity in
predicting serious
reactions
• Dividing the dose of
vaccine is also not
required because most
even severely egg
allergic patients can
tolerate the full vaccine
dose without reaction

Egg-allergic patients and
Influenza vaccinations
• 27 published studies
• 4172 patients with egg allergy received
4729 doses of inactivated influenza vaccine
• Including 513 with severe allergy who
uneventfully received 597 doses
No cases of anaphylaxis
Very low amount of egg protein present in vaccine

Background:
1. Skin test might not be necessary if IIV contains
low amount of ovalbumin
1. Individual manufacturers produce 18-145 lots of IIV/season
Objective
1. Determine ovalbumin content in influenza vaccines
2. Determine the lot-to-lot variability within a manufacturer
Method: Ovalbumin ELISA kit
McKinney K. et.al. J Allergy Clin Immunol 2011;127:1629–32

There is still uncertainty with lot-to-lot variability
and variability from year to year and
manufacturer to manufacturer

Prevention and control of seasonal influenza with vaccines. Recommendations of ACIP.
MMWR Morb Mortal Wkly Rep 2013;62:1-43

Two new IIVs not grown in eggs have been
approved for patients ≥18 years
Flucelvax: virus propagated in cell culture
FluBlok: recombinant hemagglutinin proteins produced in an insect cell line

No published studies on the safety of LAIV in
recipients with egg allergy, guidelines recommend
the use of IIV in these patients

Recommendations regarding influenza vaccination of
persons who report allergy to eggs- US-ACIP,2014–15 influenza season

“ The only precaution is administration in
a setting where anaphylaxis can be recognized
and treated and patients should remain under
observation for at least 30 minutes
after vaccination ”

Egg-allergic patients and vaccinations
• Other vaccines containing egg protein,
particularly yellow fever, it is still
recommended to test the vaccine before
administration. In case of positive
testing, the vaccine can be administered
in graded doses

Allergy to influenza vaccine
• Additional evaluation is appropriate,
including skin testing with the vaccine
and vaccine ingredients.
• If positive skin test, vaccine can be
administered in multiple divided doses
or can be withheld

In summary
• Overview of vaccine adverse events
• Type of reactions
• Potential allergens in vaccines
• Diagnosis and management

Take home messages (1)
• Mild local reactions and fever after
vaccinations are common and do not
contraindicate future doses
• Anaphylaxis to vaccines are rare and should
be further evaluated
• If the test are negative, subsequent doses can
be administered in the usual manner but
under observation

Take home messages (2)
• If the test are positive and the patient
requires subsequent doses, the vaccine can
be administered in graded doses under
observation
• Some non-anaphylactic reactions to vaccines
might also require evaluation, but only a few
are contraindications to future doses

Adverse reactions to vaccines for infectious diseases

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