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  • Updated 01.23.2021
  • Released 07.04.2018
  • Expires For CME 01.23.2024

Neurologic complications of vaccination

Introduction

Overview

Serious neurologic complications of vaccination are rare. Unfortunately, many associations between vaccination and putative neurologic complications have been asserted without sufficient objective data to establish a causal relationship. Most patients with vaccine-associated neurologic complications recover fully, although rare poor outcomes are recognized. Reported neurologic complications of vaccination have included headache, postvaccination (“needle-stick”) syncope, febrile seizures, encephalomyelitis, transverse myelitis, meningitis, polyneuritis, and macrophagic myofasciitis. This article reviews the neurologic complications of vaccines in general, as well as specific vaccines in particular, and also addresses special situations (eg, vaccination of patients with multiple sclerosis).

Key points

• Serious neurologic complications of vaccination are rare.

• Unfortunately, many associations between vaccination and putative neurologic complications have been asserted without sufficient objective data to establish a causal relationship.

• Most patients with vaccine-associated neurologic complications recover fully, although rare poor outcomes are recognized.

• Reported neurologic complications of vaccination have included headache, postvaccination (“needle-stick”) syncope, febrile seizures, encephalomyelitis, transverse myelitis, meningitis, and polyneuritis.

• Postvaccination encephalomyelitis usually occurs 10 to 14 days after vaccination, but it may occur from 7 to 21 days after vaccination.

• Headache, vomiting, drowsiness, and fever are often the first symptoms observed in postvaccination encephalomyelitis, with severe cases progressing to include disorientation, confusion, stupor or coma, paralysis, incontinence, urinary retention, and seizures.

• Case-fatality rates for postvaccination encephalomyelitis vary considerably, from approximately 10% to 50%. Death can occur suddenly, usually within a week of onset of symptoms.

• Approximately 25% to 30% of all survivors of postvaccination encephalomyelitis have some residual neurologic defect.

• Vaccination-proximate febrile seizures represent only a small proportion of all febrile seizure hospital presentations, and vaccination-proximate febrile seizures have the same outcomes as other febrile seizures.

Historical note and terminology

Vaccines are dead or inactivated organisms or purified products derived from them that are administered to a person (or livestock or pet animal) to induce a beneficial immune response that will provide protection against infection with corresponding virulent organisms.

Several types of vaccine have been employed, including different types of whole-agent and partial-agent (subunit) vaccines and live-recombinant vector vaccines.

Whole-agent vaccines were the first vaccine types employed against communicable diseases, and these include inactivated and live-attenuated vaccines. Inactivated vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation. Live-attenuated vaccines contain live, attenuated microorganisms; many of these are active viruses (or less commonly, bacteria) that have been cultivated under conditions that disable their virulent properties or that use closely related but less dangerous organisms (eg, vaccinia virus for smallpox vaccination) to produce a broad immune response. Attenuated vaccines typically provoke more durable immunological responses than inactivated vaccines and are the preferred type for healthy adults. However, live-attenuated vaccines may not be safe in immunocompromised individuals and may on rare occasions mutate to a virulent form (reversal of attenuation) and cause disease.

In contrast to whole-agent vaccines, partial-agent (or subunit) vaccines are derived from some fraction of the microorganism, such as acellular protein components, inactivated toxic compounds produced by the microorganism (toxoid vaccines), capsular polysaccharides, or capsular polysaccharides covalently bound to a protein carrier to increase immunogenicity (conjugate vaccines).

More recently, live-recombinant vector vaccines have been introduced. These occupy a middle category, in that subunits of the target pathogen are made using recombinant DNA technology, reproduced using another viral backbone.

Table 1. Vaccines by Category, Type, Organism Category, and Disease

Vaccine category

Vaccine subtype

Organism category

Disease

Notes and comments

Whole-organism

Inactivated

Virus

Hepatitis A

Influenza

“Flu shot” made from highly purified, egg-grown viruses

In most countries, since the 1970s, whole-virus vaccines have been replaced by less reactogenic split-virus vaccines and subunit vaccines.

Japanese encephalitis

Vero cell-derived vaccine; licensed in the United States, Europe, Australia, and New Zealand

Polio

Salk vaccine (injection)

Rabies

Nerve tissue vaccines (Semple and Fuenzalida) can induce severe adverse reactions and are less immunogenic; now outdated they are still used in a limited and decreasing number of developing countries.

Cell culture vaccines include human diploid cell vaccine that contains inactivated Pitman-Moore L503 or Flury strain of rabies virus grown on MRC-5 human diploid cell culture. Other cell culture vaccines include purified chick embryo cell vaccine, purified Vero cell rabies vaccine, and primary hamster kidney cell vaccine.

Embryonated egg vaccines: Purified duck embryo vaccine uses duck embryo cells as a substrate. This vaccine contains thiomersal.

Tick-borne encephalitis

FSME-Immun (Austria), Encepur (Germany), TBE-Moscow (Russian Federation), EnceVir (Russian Federation)

Bacteria

Cholera

WC-rBS, killed whole-cell monovalent (O1) vaccine with a recombinant B subunit of cholera toxin 37

WC, killed modified whole-cell bivalent (O1 and O139) vaccine

Pertussis

Typhoid

Live-attenuated

Virus

Influenza

Seasonal flu nasal spray and 2009 H1N1 flu nasal spray

Japanese encephalitis

Licensed in China

Measles

Monovalent

Mumps

Monovalent

Measles, mumps, rubella

MMR combined vaccine

Measles, rubella

MR combined vaccine

Measles, mumps, rubella, varicella

MMRV combined vaccine

Polio

Sabin vaccine (oral)

Rotavirus

Rotarix and RotaTeq

Rubella

Monovalent

Smallpox

ACAM2000 has replaced Dryvax smallpox vaccine

Shingles or zoster (varicella zoster virus)

Lyophilized preparation of live-attenuated Oka/Merck strain (Zostavax)

Varicella (Chickenpox, varicella zoster virus)

Zoster Vaccine Live (ZVL) - Live-attenuated Oka strain, propagated in MRC-5 human diploid cells (Varilix and Varivax vaccines)

Yellow fever

Two 17D substrain vaccines are manufactured today: 17DD (manufactured in Brazil and used in South America) and 17D-204 (YF-VAX; Manufactured outside of Brazil, including the US)

Bacteria

Anthrax

Russian vaccine containing spores from attenuated strains of B. anthracis

Typhoid

Oral

Tuberculosis

BCG vaccine

Partial-organism (subunit)

Virus

Split virus

Influenza

The split-virus vaccine uses detergent to dissociate the viral lipid envelope, exposing all viral proteins and subviral elements

Protein subunit

Hepatitis B

Hepatitis B surface antigen

Protein subunit

Hepatitis E

Licensed in China

Based on a recombinant 239-amino-acid-long peptide (a portion of the capsid protein), which is expressed in E. coli, and purified.

Protein subunit

Human papillomavirus

Highly purified virus-like particles (VLPs) that are the protein shells of the human papillomavirus virus (major capsid protein L1). VLPs contain no viral DNA, so cannot infect cells, reproduce, or cause disease.

Gardasil 4v and 9v are produced using recombinant Saccharomyces cerevisiae (bacteria), and Cervarix 2v are produced in a recombinant Baculovirus expression vector system.

Protein subunit

Influenza

Hemagglutinin and neuraminidase antigens have been purified by removal of other viral components.

Protein subunit

Meningococcal disease

MenB-FHbp is a bivalent vaccine consisting of 2 different recombinant lipidated factor H binding protein (FHbp) antigens.

MenB-4C is a multicomponent vaccine consisting of 3 recombinant proteins.

Protein subunit

Shingles or zoster (herpes zoster virus)

Zoster vaccine recombinant, adjuvanted (Shingrix)

Bacteria

Acellular fraction

Anthrax

Anthrax vaccine adsorbed licensed in United States, and Anthrax vaccine precipitated licensed in United Kingdom

Acellular fraction

Pertussis

Toxoid

Diphtheria

Monovalent

Toxoid

Tetanus

Monovalent

Toxoid

Diphtheria and tetanus

Combination toxoid vaccines:
DT, used for primary immunization and boosting in children;
Td, used for boosting and primary immunization in adolescents/adults

Toxoid (DandT), Acellular fraction (P)

Diphtheria, pertussis, and tetanus

DTP combinations:
Initial DTP combinations contained whole-cell pertussis antigens. Frequent occurrence of minor local reactions and less common severe reactions of whole-cell pertussis vaccine led to the development of acellular vaccines.

Polysaccharide

Meningococcal disease

Monovalent (A or C), bivalent (A, C), trivalent (A, C, W135), and quadrivalent (A, C, W135, Y) formulations.

The quadrivalent MPSV4 vaccine is used in the United States.

Polysaccharide

Pneumococcal disease

PPSV, 23-valent vaccine

Conjugate

Haemophilus influenzae type b

Hib

Conjugate

Meningococcal disease

MenACWY-D, MenACWY-CRM, Hib-MenCY-TT

Conjugate

Pneumococcal disease

PCV, 7-, 10-, and 13-valent vaccines

Live-recombinant vector

Virus

Dengue

CYD-TDV is a live attenuated tetravalent chimeric vaccine made using recombinant DNA technology using a yellow fever vaccine virus backbone vector that expresses envelope proteins of dengue viruses

Live-recombinant vector

Japanese encephalitis

Genetically engineered chimeric vaccine that combines protective antigenic determinants of attenuated SA14-14-2 JE strain with yellow fever vaccine strain 17D (YF 17D) virus as a vector backbone.

Licensed in Australia and some Asian countries

mRNA

Virus

SARS-CoV-2

Pfizer-BioNTech COVID-19 vaccine; Moderna’s COVID-19 vaccine

Note: Some diseases have multiple vaccines of different types that are currently being used.

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