Immunisation of Experimental Animals


Effective vaccines are urgently required for some of the major killer diseases such as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, cancer, as well as for emerging infectious diseases such as Ebola and the coronavirus infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This challenge can only be realised through a better understanding of the interplay between pathogen (or tumour) and the host's immune system. While epidemiological surveys and various in vitro studies provide useful leads, experimental animals are powerful tools for the manipulation of the immune response in vivo and remain central to our understanding of the body's response to infection. They afford a means of analysing the different roles played by the various components of the immune system in providing protection against disease and of devising methods of enhancing and accelerating this protection by immunisation.

Key Concepts

  • Proteins, polysaccharides or glycoconjugated antigens may lack the desired pathogen‐associated molecular patterns (PAMPS) that are necessary to activate the innate immune response.
  • Incorporation of antigen with defined PRR agonists is desirable for potent activation of dendritic cells that steer the response of antigen‐specific T and B cells.
  • The type of formulation, dose, site and route of administration are critical to the outcome of the immune response to a given antigen.

Keywords: immunity; vaccination; adjuvants; antiserum; T‐cell activation

Figure 1. Key events leading to the induction of an immune response. Entry of pathogen, with membrane‐associated pathogen‐associated molecular patterns (PAMPS), through external barriers sets off an inflammatory response. Pathogen is taken up by PRRs on immature DCs, which migrate to the nearest draining lymph node where they mature and present processed antigen to T cells. Antigen‐activated naïve T cells differentiate into various Th phenotypes as directed by cytokine signals and transcription factors (red arrows). This leads to antigen‐specific help to B cells for production of appropriate antibody and generation of cytotoxic T cells against the invading microorganism. These events are controlled by regulatory T cells (Treg), which prevent the activity of autoreactive T cells and participate in the control of T‐cell hyperactivity. While MHC genes influence T‐cell function, including help for antibody production by B cells, non‐MHC genes control cytokines, which regulate polarised immune responses. NB. For simplicity, this diagram does not show the development of Th9 and Tfh phenotypes. Reproduced with permission from Olive (2012) © Taylor & Francis Ltd.
Figure 2. Immunisation schedule and ensuing immune response to antigenic challenge in mice. Typical immunisation schedule (blue arrows) where a priming dose is administered in adjuvant, usually 3 weeks apart. The first (day 0) dose of antigen is administered in adjuvant with immunostimulant. Adjuvant is essential for initiating the immune response, with optimal activation of DCs. However, booster doses, intended for activation of memory cells, may be given with adjuvants that encourage a depot effect 3 weeks later provided that antibody levels have decreased substantially. Antibody titres are measured from test bleeds taken before the first dose of antigen and then at regular intervals. The immune response, depicted here as antibody titre (cellular responses show similar characteristics), is apparent by day 7 and consists mainly of the IgM subclass. IgG antibody of lower magnitude appears by day 11, a few days later. However, following boosting, the onset of IgG antibody is rapid, appearing within 3–4 days and greatly exceeds the level of IgM. The magnitude and rate of responsiveness is directly related to the number of long‐lived memory cells, hence a challenge – conceivably live infection – at day 120 results in a sharp rise in antibody titre and cellular reactivity with consequent attenuation of infection.


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Further Reading

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de Souza, Joseph Brian(Apr 2016) Immunisation of Experimental Animals. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001439.pub2]