Vaccines

last authored: October 2009, David LaPierre

 

Introduction

Vaccination, or immunization, is the administration of antigen to develop an immune response, including cellular activation and antibody production, in order to prevent subsequent infection. The term vaccine, derived from latine for cow, was coined by Pasteur in honour of Edward Jenner's work with cowpox.

 

 

 

Specific Vaccines

Viruses

Bacteria

 

 

Vaccine Schedules

Premature infants should receive vaccinations based on their chronological age, regardless of birthweight, not calculated age. THe exception is hepatitis B, which should not be given under 2 kg.

 

Various locales have differing vaccination policies. Some of these include:

  • Nova Scotia, Canada
  • CDC

Nova Scotia, Canada

 

Childhood

  • DaPTP-IPV-HiB (Pentacel) - 2,4,6, 18 months
  • pneumo. conj. - 2,4,6, 18 months
  • men c conj - 12 months
  • varicella - 12-15 months
  • MMR - 12 months, 4-6 years
  • flu - 6-23 months
  • DaPTP - 4-6 years
  • hepatitis B: 3 doses

Adulthood

  • Td: every 10 years

CDC

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Definitions

antigen: substance to which specific antibodies form

hapten: protein conjugates to vaccine antigen to enhance
immune response

adjuvant: substance increasing immunogenicity (ie alum)

preservative: substance to reduce contamination
(ie thimerosol, phenol)

stabilizer: substance to maintain integrity during temperature
change (ie gelatin, sucrose)

manufacturing residual: inactivating agent (ie formaldehyde)
or cellular material (ie egg protein)

Types of Vaccines

 

 

 

 

 

 

 

 

 

 

 

 

  • live vaccine
  • killed vaccine
  • isolated protein vaccine
  • polysaccharide vaccine
  • DNA vaccine
  • passive vaccine

Live vaccines

  • Most effective vaccine, made from live pathogens that have been somehow attenuated to make them non-pathogenic but can still replicate
  • Effectiveness due to the fact that organism persists for longer periods, and multiple epitopes present
  • Can, on rare occasions, revert to become pathogenic again

Live vaccines in use include oral polio (primarily in developing countries), varicella, MMR, yellow fever, oral typhoid, and BCG against TB; used in confined populations during outbreaks.

Killed Vaccines

Killed vaccines are safer, but less effective than live vaccines; booster doses often required, along with adjuvants. They offer many epitopes, in contrast to sub-unit vaccines

Examples include: influenza, rabies, whole cell pertussis.

Isolated protein vaccines (subunit)

Isolated vaccines are well-characterized, customizable. Decreased effectiveness require adjuvants, such as aluminum, to enhance inflammatory response. Liposomes may circumvent need for adjuvants by enhancing APC uptake.

Isolated vaccines essential for immunization against toxins (toxoids), ie tetanus and diptheria. They are also used against hepatitis B and pertussis.

Polysaccharide vaccines

One might imagine IgG response requires T cell response and class switch, which occurs only with peptide antigen. However, PS vaccines do work over age 3, likely through formation of chimeric haptens.

Conjugated vaccines of capsule proteins for H. influenzae (Act-Hib) and S. pneumoniae (Prevnar) work for infants 2 months and up, through require boosting.

DNA (Vector) vaccines

DNA vaccines use use hybrid DNA, with a live virus/bacterial vector and an inserted gene of interest. These have a small spectrum of antigens, and have this far led to a disappointing response.

Passive vaccines

Passive vaccines contain immunoglobulins designed to kill or attenuate pathogen. These include human blood products or monoclonal antibodies. The effect of injecting immunoglobulin was first discovered in the late 1800s. Since then, Passive immunization has become standard practice in many cases. They protect for approximately one month.

 

Passive immunizations are prepared from the pooled plasma of thousands of donors, representing a sample of anitbodies that respond to a broad variety of pathogens. A gram of intravenous immunoglobulin (IVIG) may contain 1018 molecules of IG - mostly IgG and may represent up to 107 different antibody specificities. Patients often receive 200-400 mg per kg, meaning a 70 kg man would receive 14-28 g every 3-4 weeks.

 

IVIG is treated exhaustively with solvents and detergents to reduce the risk of infectivity and to reduce aggregates that might trigger massive activation of the complement pathway and subsequent anaphylaxis.

 

One of the most important uses of administered antibody is the recruitment of the complement pathway to destroy pathogens. Opsonization will target pathogens for phagocytosis, and toxins will be neutralized. Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells also occurs.

 

Settings where IVIG is used include:

  • IgG is given to immunocompromized patients both IM and IV.
  • RSV IgG given to premature babies
  • if risk of tetanus without recent booster
  • rabies if bitten
  • anti-venom

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Vaccine Safety and Contraindications

As with almost all health interventions, vaccines carry benefits and risks. As they are usually given to healthy people to prevent disease, they are held to a higher standard of safety.

 

Immediate Reactions

The most common adverse event is local injection site pain, lasting <48 hours. The MMR is especially painful.

Systemic reactions such as fever are less common, and must be reported by physicians to ensure safety for others.

Causality of other events is more difficult to prove.

 

Many people are concerned about the safety of vaccines.

unlikely links:

 

Minor illnesses, such as the common cold, with or without fever, are NOT contraindications for immunization. However, moderate or severe illness precludes vaccination.

 

Other contraindications include:

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Difficulty with Vaccine Design

Many pathogens resist killing following with vaccines.

Many parasites have different stages during their life cycle, each with various antigens. Effective vaccines would need to address various stages.

 

 

Resources and References