Background: Respiratory Syncytial Virus infections are world widely discussed the last few years as underestimated medical burden in adult medicine. Regarding the recent development of new vaccines against this disease it is necessary to evaluate the vaccination program which was started, e.g. in Germany, in clinical setting. While evaluating this vaccination strategy in Germany costs of 200000 Euros per gained QUALY could be calculated with taking the actual German vaccination recommendations into account (all over 75 years of age, very ill over 60 year old peolple and all over 60 year old nursing home residents). Therefore it is necessary to have an critical eye on the real infectious burden and protective immuncompetence of a group of people at high risk (immunocompromised mostely DMARD treated patients with rheumatic diseases) before and while vaccination program started.

Objectives: Evaluating the baseline immunity of patients out of a rheumatologic setting and the course of immunity calculated by antibody development of IgA and IgG over time. In dividing into two groups a) below and b) above 75 years of age the evaluation of vaccination gained antibody development of IgA and IgG and the immuncompetence with or without vaccination has to be assessed and estimated.

Methods: Detecting IgA and IgG antibody levels from midst of 2024 on (before vaccination program started) and approximately 1 year later. Differentiation into groups with or without vaccination and calculating different clinical important bullets, like actual immunity before and while vaccination program started, waining antibody levels over time (simplified by waining antibody level per day, per week, per month), gain of antibody levels by new infection/ vaccination, dividing these data into group of below and above 75 years of age. 396 patients with age of over 60 have been tested for IgA and IgG levels against RSV (serological) first in 2024 (261 patients below 75 and 135 patients 75 + years of age). Out of 25 patients below 75 years of age which have been tested a second time for IgA and IgG levels 22 patients have been not vaccinated or infected. Out of 87 patients with 75 + years of age which have been tested a second time for IgA and IgG levels 84 patients have been not vaccinated or infected. Sufficient data analysis regarding the 5 patients which were vaccinated and only one patient which got infected was statistically not possible. Therefore examples out of this patients have to be shown.

Results: Before Vaccination program (midst of 2024): Median IgA: 0,7 ratio, Median IgG levels 105 RE/ml over all 396 patients, which means an avarage timespan after last infection of at least 12 months passed by (norm parameters IgA positivity ratio 0,8 +, IgG positivity RE/ ml 16 +). In 65-74 year old patients (22 patients, Median age 74,2) without infection/ vaccination after a Median of 350,5 days Median IgA ratio went from 0,7 to 0,55, Median IgG went from 109 to 71,75. This means approximately waining IgG levels of 0,1 RE/ ml per day, 0,7 RE/ ml per week and 3,2 RE/ ml per month and waining IgA ratio of 0,0004 per day, 0,003 per week and 0,012 per month. In 75 + year old patients (84 patients, Median age 80,3) without infection/ vaccination after a Median of 336 days Median IgA ratio went from 0,7 to 0,6, Median IgG went from 104,5 to 81,7 RE/ ml. This means approximately waining IgG levels of 0,068 RE/ ml per day, 0,475 RE/ ml per week and 2,036 per month and waining IgA ratio of 0,0003 per day, 0,002 per week and 0,089 per month. As example one vaccination patient (age at vaccination 75,3 years) without previous insufficient immunity of IgA ratio 0,1 and IgG level of 0 RE/ ml gained a ratio of 0,1 IgA and 64,1 RE/ ml IgG level 201 days after vaccination. As another example one vaccination patient (age at vaccination 81,9) with sufficient prevacciantion immunity of IgA ratio 2,9 and IgG level of 82,1 RE/ ml had no gain in immunity after 83 days seen by tested values of IgA 2,4 ratio and 76,8 RE/ ml IgG level.

Conclusions: Taking the high prevalence of a Respiratory Synzitial Virus as an example for high infectious diseases into account, the consideration of false positive and negative test rates and related statistical biases (i.e., overestimation of the “vaccine effectiveness” reported in these study designs), and the predominant use of test-negative study designs as the gold standard in post-marketing has to lead to a more individualized vaccination strategy to be choosen. This is all the more important because negative test designs are not determining biological vaccine effectiveness, but rather the utilization of the healthcare system, which, strictly speaking, is almost independent of the disease being tested. In the case of RSV vaccination, vaccine costs also play a significant role in the overall assessment, especially considering that and taking various factors into account the actual RSV vaccination can incur high costs if it is not adapted into more individualized vaccination decisions. Our results showed that waining immunity after at least one year after last infections (IgA ratio 0,7) takes a long time of approximately 2,5 years to reach the Deltavalue which could be gained again by one vaccination in insufficient preimmunized people (which underlines the 3 saison efficacy statement of the actual vaccines quite good). In sufficiently preimmunized people there might be no immunogenicity effect. Wether any overall clinical effect could be shown for RSV vaccination is only statistically possible sufficiently by cohort studies and not sufficiently enough in negative test design. Although the new RSV vaccines seem to have a more immunogenicity gaining effect as natural diesease itself by using the prefusion protein as the antigen, the results of this study showed that current vaccination strategy has to be adapted to a much more individualized strategy, also taking into account side effects like Guillain Barré syndrome.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.