Do we finally have a “correlate of protection…
The vaccines that we know are used to prevent infectious diseases. They are expected to prevent infection by a pathogen, or failing that, to prevent the development of a disease or its most serious manifestations. Evaluating their effectiveness, especially during the development phases, can be difficult and time-consuming. It is easier to assess their immunogenicity, ie their ability to induce an immune response which results in the appearance of antibodies and specialized cells. To show that this response is protective, when it is not possible to experimentally infect volunteers (we speak of a “challenge”, reserved for diseases that are certainly benign), it is necessary to compare the risks of infection and disease between groups of vaccinated and unvaccinated people who will be naturally exposed to infection. If there is little transmission, if other measures are used simultaneously to limit transmission, or if part of the population is already protected or not exposed, when hundreds or thousands of cases are sometimes necessary to establish reliable statistics, evaluating the effectiveness of a vaccine can take months or years. After its commissioning, the comparison with other vaccines or between batches for the same product must also be considered and be able to be carried out quickly.
Another situation in which it is desired to have a means of evaluating the protection conferred by a vaccine is that of individual cases where this protection is necessary and must be verified, whereas revaccination is not possible or desirable.
The covid 19 pandemic is continuing, in successive waves, and the appearance of variants leads to the proposal of new vaccines which must be able to be quickly evaluated and used. The protection that these vaccines can provide may differ depending on the background and condition of the people for whom they are intended.
We therefore seek to have correlates of protection, that is to say biological markers preferably simple to highlight, detectable quickly after vaccination, indicating that immunity against the disease has developed and that it provides effective protection against its manifestations in the event of contamination. But identifying such a marker is not easy and must be considered on a case-by-case basis: what is valid for a disease or a vaccine cannot be transposed to any other situation. We do know, however, because it has been shown after long studies for different disease/vaccine systems, that certain antibodies produced after vaccination and relatively easy to quantify in the laboratory are indeed indicators of protective immunity.
To establish protection, vaccines stimulate the immune system, provoking two types of response, one humoral (antibodies), the other cellular (T lymphocytes, capable, among other things, of killing foreign or modified cells). We know how to study these responses, but it is not easy to identify which, qualitatively and quantitatively, will be the mark of a state of protection. As it is relatively easy to highlight and measure antibodies, it is to them that we are interested in priority. When it comes to protection against an infectious agent, two categories of antibodies are sought:
- The set of antibodies capable of binding to the antigens of the agent (“ binding antibody ”): these are the easiest to analyze, using various automated methods, including the classic ELISA. We are then interested in antibodies that recognize one or a few antigens that are particularly exposed and important for infection, such as the S protein of SARS-CoV-2. In any immune response, these antibodies are numerous and diverse, and not all contribute to establishing protection.
- “Neutralizing” antibodies which, in laboratory tests, have the effect of preventing the infection of cells in culture by the agent against which they are produced. These tests are much more complex than the fixation tests, but they are mastered by many laboratories and they have a very high specificity. They highlight mechanisms that probably contribute to the protection against infection in infected people, but a parallel cannot be systematically drawn between the presence and concentration of these antibodies in the blood and the level of protection.
Whatever the type of antibody in which one wishes to be interested, the “correlation” between these antibodies and a level of protection must be demonstrated. This requires long studies, during which the infection must sometimes be provoked (in animals or in humans), the immune response is analyzed according to the manifestations and prognosis of the infection, the effects of selected antibodies administered before or after infection, the relationship between vaccine efficacy and marker concentration is quantified. In an article published in the New England Journal of Medicine, P. Gilbert et al. expose the state of accumulated knowledge on the vaccines used against covid 19. They come to the conclusion that the data are now more abundant for covid than for most other vaccine-preventable diseases, and that they lead to consider that neutralizing antibodies are good correlates of protection for available vaccines. They can be used for making decisions concerning these vaccines (initial vaccination, target and frequency of revaccinations), which thus do not have to wait for the results of protection studies. The authors emphasize, however, that the correlates of protection remain to be identified for a number of situations: infection by viral variants, protection of particular population groups (such as those already infected), vaccines using different technologies, aspects of infection against which protection is sought.
The scope of the announced correlate is therefore limited. However, it could be enough to base certain decisions that must be taken quickly to deal with an epidemic that is still ongoing and whose evolution is unpredictable.
#finally #correlate #protection..