Talk Morgan Forums Community The Malvern Arms Vaccination update

There are two inter-related facets of the immune response, the so-called humoral immune response whose effector arm are antibodies produced by B lymphocytes and the cell mediated immune (CMI) response whose main effector arm are CD8 positive cytotoxic T lymphocytes usually referred to as CTLs. As has been indicated by others, the job of antibodies is to attack viruses before they enter cells of their host organism and begin replicating and the main way in which they achieve this is to bind to the invading virus particles and block their entry into susceptible host cells. By contrast the job of CTLs is to screen the surface cells for any evidence of the expression of viral protein fragments on the surface of the cell in association with class 1 Major Histocompatability Antigen (MHC) molecules (these are proteins expressed on the surface of all our cells with the exception of red blood cells and are involved in the self vs non-self recognition by the immune system and so are important in so-called graft vs host disease that is so important in organ transplantation). When a CTL detects fragments of viral proteins in the context of Class 1 MHC it triggers the release of cytolytic factors that kill the virus infected cell thereby blocking completion of the virus replication cycle and so the release and spread of progeny virus particles. Because of the involvement of MHC molecules in this recognition process CTLs cannot be used for so called passive immunisation except between identical twins whereas you will have seen reports of passive immunisation being used where convalescent sera, containing anti-viral antibodies, taken from people who have recovered from a virus infection is used to either treat those newly infected with the virus or to provide short-term (3-6 months) protection against infection and disease development. So antibodies operate to attack the virus before they enter cells of the host and start to multiply and are transferable between people whereas CTLs attack virus infected cells to block the spread of the virus within the host and are effectively restricted in their action to the person in which they generated. The other major difference between these two effector arms of the immune response lies in their speed of development and longevity. So when we are infected for the first time by a virus, a specific CTL response to that virus will develop very rapidly (just days) and their varying effectiveness in an outbred host such as humans is seen as being largely responsible for governing if and how seriously clinical disease develops following an acute infection. However, in the absence of continuing viral stimulation, the CTL response will wane away relatively quickly to background so called memory levels in 3-6 months. Consequently, historically triggering a strong CTL response has not been the focus of efforts to develop effective vaccines against a new viral pathogen, not only because the response itself has until relatively recently been much more technically demanding to measure than an antibody response to a vaccine, but also because its short duration means that any vaccine dependent on it would only give protection for a few months before re-vaccination would be needed to maintain protection.

The situation for the antibody response is more complex. First, there are different structurally and functionally classes of antibody, with three classes, IgM, IgA and IgG being involved in responding to infection. Like CTLs, development of the IgM is rapid (days) and wanes away within 3-6 months in the absence of re-stimulation. So while detection of an elevated igM response against a specific pathogen is widely used as an indication of a recent infection by said pathogen, the triggering of a strong igM response is not the focus of attention when developing new vaccines. The IgA response is slower to develop (typically 2-4 weeks) and much longer lasting (can be years) but IgA molecules are localised predominantly to what are termed mucosal surfaces ie: the gastro-intestinal tract, the respiratory tract and the uro-genital tract. Consequently, stimulating a strong IgA response has become a focus for vaccines that target viruses whose primary site of infection/replication is in mucosal tissues. Finally there is IgG, the main circulatory antibody. Like IgA it is slow to develop (2-4 weeks) to its maximum levels and is also long lasting. Because it localises to the circulatory system and has a long half-life, often years and sometimes decades in terms of providing protection from disease, it is the type of antibody that is most sought in response to vaccine based immunisation.

Turning finally to your apparent absence of an antibody response following immunisation with the AZ vaccine. Yes it may be that your serum igG levels take longer than the norm to develop. It is also that you are a non-responder to the particular vaccine formulation that you have received, for example approximately 20% of people did not give a protective antibody response to the first hepatitis B virus vaccine developed. However subsequent work on developing the vaccine formulation has reduced the level of non-responders. It is also the case that the fact that an individual responds poorly/not at all to one vaccine does not necessarily mean that they will show a similar lasck of response to other vaccines. So just because you have not as yet shown a detectable antibody response to the AZ vaccine does not mean that you should start thinking about serious changes to your lifestyle.

I hope that the above is in formative and helpful.

Stay safe.

Malcolm