MicrobiologyBytes: Virology: Vaccines Updated: April 8, 2009 Search

Prevention and Treatment of Virus Diseases: Vaccines

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There are two aspects to the prevention and treatment of virus diseases:
  1. Prevention: Vaccination and public health measures

  2. Treatment: Antivirals
Most of the damage to cells in virus infections occurs very early, often before clinical symptoms of disease appear. This makes treatment difficult, therefore prevention is better than cure!

Vaccination

Although prevention of infection is much the preferred option, post-exposure vaccines can be of great value in modifying the course of some virus infections e.g. rabies.
To design effective vaccines, we need to understand immune response to virus infection.

Cell Mediated Immunity: T cells:

Cell mediated immunity is particularly important in virus infections.
CD8 cells, Cytotoxic T Lymphocytes or CTL cells.The details of these responses will be familiar to you from elsewhere. Agammaglobulinaemic children are not especially at risk of virus infections such as measles. In contrast if they lack T cells then measles is fatal. T cells are able to recognise virus infected cells early in the infection process.

MHC Class I is present on all nucleated cells with the exception of neurons. They present endogenous (intracellular) antigens including virus ones i.e before virus is released from a cell. T cell receptor can recognise antigen-MHC I complexes.
MHC Class I is present on antigen presenting cells such as macrophages T and B cells. These cells take up exogenous (extracellular) antigens ie they can only present virus antigens from another cell, after replication and release.
Suggests that MHC I is more important in clearing virus infections. If the MHC I system is knocked out then animals can still clear virus infections but less quickly. Presumably virus replication occurs and exogenous virus proteins are processed by MHCII cells.

Humoral Immunity: B Cells:

Antibodies, although less important do play a role in virus infections. They can clump viruses, coat them preventing infection, activate complement. They can also recognise infected cells, but late in an infection.

The ideal vaccine therefore evokes both B and T cell immunity and must contain the epitopes to do so. It will not itself cause disease. To be effective, not necessary to get 100% uptake of vaccine - "herd immunity" will break the spread of a virus; this strategy is most effective where there is no alternative host, e.g. measles.

Vaccination Strategies

There are three basic types of vaccine:

1) Sub-unit Vaccines

The newest type; completely safe, except for rare adverse reactions. Unfortunately, they also tend to be the least effective. Problems:
a) Synthetic Vaccines
Not very effective. Great potential. None currently in use.
b) Recombinant Vaccines
Better than above - some success has already been achieved:
HBV - now produced in yeast.
c) Virus Vectors
The idea is to utilize a well-understood, attenuated virus to present antigens to immune system, e.g:
Hard to produce, safe???, none successful yet - lots of trials underway.

2) Inactivated Vaccines

Method of production - exposure to denaturing agent - results in loss of infectivity without loss of antigenicity.

Advantages:

Disadvantages:

3) Live Virus Vaccines

The use of virus with reduced pathogenicity to provide immune response without disease. May be naturally occurring virus (e.g. Jenner, cowpox, 1776 (Variolation)) or artificially attenuated (oral poliovirus vaccine (OPV)).

Advantages:

Disadvantages:

Administration

  1. Oral: o
  2. Subcutaneous or scarification: sc
  3. Intramuscular: im

Adjuvants

These enhance the immune response and are included in inactivated and subunit vaccines e.g aluminium hydroxide. This is considered safe for human use.

Human Antiviral Vaccines Currently in Use:

Virus: Administered: Attenuated: Inactivated: Recombinant / Sub-unit:
Hepatitis A im   X  
Hepatitis B im/sc     X
Influenza im   X  
Japanese B encephalitis sc   X  
Measles, Mumps, Rubella (MMR) im X    
Poliovirus o/im X X  
Rabies im   X (X)
Smallpox sc X    
Tick-borne encephalitis im   X  
Varicella-Zoster im X    
Yellow fever sc X    

UK Vaccination schedule:

The UK Department of Health publishes The Green Book, the latest information on vaccines and vaccination procedures for all the vaccine preventable infectious dieseases that may occur in the UK. In particular it deals with those immunisations that comprise the routine immunisation programme for all children from birth to adolescence.

Read the latest edition here

Topics include: Immunity and how vaccines work | Consent | Storage | distribution and disposal of vaccines | Immunisation procedures | Immunisation by nurses and other health professionals | Contraindications and special considerations | Immunisation of individuals with underlying medical conditions | Vaccine safety and adverse events following immunisation | Surveillance and monitoring for vaccine safety | Vaccine Damage Payment Scheme | Immunisation schedule | Immunisation of healthcare and laboratory staff | Anthrax | Cholera | Diphtheria | Haemophilus influenzae type (Hib) | Hepatitis | Hepatitis | Influenza | Japanese encephalitis | Measles | Meningococcal | Mumps | Pertussis | Pneumococcal | Polio | Rabies | Rubella | Smallpox and vaccinia | Tetanus | Tick-borne encephalitis | Tuberculosis | Typhoid | Varicella | Yellow fever.

How are live vaccines prepared ?

Viruses were grown in animal cells but human diploid cells now commonly used. These are screened for all known viruses. However biological additives are required for their growth e.g. foetal calf serum. There is always the risk therefore of contamination with a biological agent. [e.g. the current BSE scare]. Cultures are seeded from safe virus stocks. The vaccine is only ever one or two passages removed from the seed to minimise the chances of virulence returning.

Passive immunisation

Normal pooled human immunoglobulin fraction. Heat treated to destroy viruses. Considered as safe. Examples of use:
Prevention of Hepatitis A.
Prevention or modification of measles in the immunocompromised who have been in contact with a case.
HBV Ig is coadministered with the vaccine to provide rapid protection after say a needlestick injury. Rabies Ig immediately after exposure.
Varicella Zoster Ig to the immunosuppressed and leukaemic.
Lassa Fever convalescent plasma is therapeutic.

Problems

Sensitisation, reversion, rare possible complications. Attenuated vaccines not given to pregnant or immune compromised.
Developing effective vaccines to some viruses is proving very difficult e.g. influenza, common cold viruses, HIV-1, herpes, papilloma and more. Common problems include the existence of many serotypes, antigenic drift and shift.

The Future?

Success stories:

Detailed notes for these documents can be found in Chapter 6 of Principles of Molecular Virology.

CoverStandard Version: The 4th edition contains new material on virus structure, virus evolution, zoonoses, bushmeat, SARS and bioterrorism, CD-ROM with FLASH animations, virtual interactive tutorials and experiments, self-assessment questions, useful online resources, along with the glossary, classification of subcellular infectious agents and history of virology. (Amazon.co.uk)

Cover Instructors Version: The 4th edition contains new material on virus structure, virus evolution, zoonoses, bushmeat, SARS and bioterrorism, CD-ROM with all the Standard Version content plus all the figures from the book in electronic form and a PowerPoint slide set with complete lecture notes to aid in course preparation. (Amazon.co.uk)

© MicrobiologyBytes 2009.