Vaccines Dr T. Espanol Immunology Unit University Hospital Vall d´ Hebron Barcelona

Effective vaccines: rapid decrease in infections in the general population

If protective immune response levels are high in the general population, the possibility of dissemination of an infection is low. For this reason it is so important to follow the immunisation programmes until the infection can be considered erradicated Measles cases / protection

Innate response / inflammation Specific response Red cells Platelets Specific response

How and where the infections enter the body Distribution and recirculation

A main characteristic of the immune response is its ability to recognise antigens in any part of the body and distribute effector cells and antibodies throughout the organism

Most cells of the immune response recirculate throughout the body and in lymph nodes they mature to produce antibodies or cytotoxic cells that leave the lymph nodes for any part of the body

Acute inflammatory signs: fever oedema swelling....

Innate responseSpecific T-cell response

Specific T-cell response begins with recognition of the “intruder” by monocyte/macrophages (through some receptors), and the presentation of antigens (part of the proteins) to the super-specific T-cell receptor

1st 2nd Innate response/inflammation is essential to elicit a specific response

The antigen is presented to the T cells to begin complex cell activation, induce several effector mechanisms, collaborate with B cells to produce antibodies and secrete cytokines that mature cytotoxic cells, etc

HLA antigens are inherited characteristics of all human cells (except red cells and the cornea) and their function is to recognise the “identity” of our cells versus foreign cells or cells with foreign antigens Correlation between some HLA characteristics and diseases

The job of cytotoxic cells is to kill the cells recognised as “foreign” (transplants) or which have foreign “particles” in the membrane (virus-infected cells)

A high proportion of plasma cells mature in lymph nodes

Immunoglobulins are proteins with several functions The Fab segment is able to recognise many different antigens

Total diversity: Ig´s T-cell receptors:

Main characteristics of the immune response: - immunological memory (used in vaccination) - high specificity (used in vaccination) - recirculation (oral vaccines) - a very high energy-consuming system

If there is a chronic inflammatory response and no antibodies to eliminate the bacteria, lesions appear in different organs

Extracellular bacteria: pneumococcus haemophilus streptococcus, etc Intracellular bacteria: tuberculosis salmonella, etc Viral infections : polio measles HIV, etc

Vaccines to produce antibodies to bacterial infections and toxins e.g. Pneumococcus, tetanus toxins  must stimulate the maturation of B cells (a T-cell collaboration is needed!) Vaccines to prevent viral infections e.g. measles, polio, HIV  must stimulate cytotoxic cells (T cells) Most of them are very effective in healthy persons. - HIV vaccine not achieved to date due to the extreme variability of the virus and because it is a retrovirus - Anti-’flu vaccines. Effective but the antigen must be changed periodically due to changes in the virus Vaccines against parasites (e.g. Malaria) very difficult to achieve Not much research has been done ( affects poor countries !!!)

Types of vaccines : Attenuated (“live “ vaccines)  BCG, measles, chicken pox... Inactivated  most anti-bacterials, polio i.m., ‘flu... Toxoids  tetanus Conjugated (polysaccharides and proteins)  Haemophilus Recombinant  Hepatitis B DNA vaccines  under development New vaccines : Human Papilloma virus  recombinant Rotavirus  attenuated

Different types of vaccines and their efficacy

Therapeutic vaccines : to stimulate the immune response to a specific microorganism that is infecting a patient with poor response - Anti-tumour “vaccines”: Use of presenting cells with incorporated tumoral antigens  to induce a stronger specific response - Immunotherapy in allergic diseases: to inhibit specific IgE synthesis with small and repeated amounts of the allergen (tolerance)

PID diseases. A molecular and genetic approach nd ed. H.Ochs et al

GENERAL RULES : - if an antibody response or a T-cell response cannot be produced, vaccines will not be useful - live or attenuated vaccines can produce the same disease in an immunodeficient or immunocompromised individual (e.g. oral polio) Vaccines against bacteria are of no use in antibody deficiency syndromes. In these cases, theoretically, vaccines against virus COULD (?) be given, but there is no way to know whether they are effective. In any event, inactivated or recombinant vaccines should ALWAYS be used !!!

Clinical focus on PID – IDF October 1998

And it is important for PID patients that national levels of protection against the majority of microorganisms are optimum.

- François G et al. Vaccine safety controversies and the future vaccination programs. Ped Infect Dis J 2005; 24(11) Ada, G. Vaccines and vaccination. N. Engl.J. Med 2001; 345: Ljungman, P., Engelhard, D., de la Camara R, et al. Vaccination of stem cell transplant recipients: recommendations of the Infectious Diseases working party of the EBMT. Bone Marrow Transplant 2005; 35: Nachman S, Kim S, King J, et al. Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants with human immunodeficiency virus type 1 infection. Pediatrics 2003; 112: Witney, CG, Farley, MM, Hadler, J. et al Decline in Invasive Penumococcal Disease after the Introduction of Protein-Polysaccharide Conjugate Vaccine. N.Engl.J.Med 2003; 348: Some references