Complexity of the Immune Response Elicited by Different COVID-19 Vaccines, in the Light of Natural Autoantibodies and Immunomodulatory Therapies.

Despite the abundance of data on the COVID-19 vaccine-induced immune activation, the impact of natural autoantibodies (nAAbs) on these processes is less well defined. Therefore, we investigated potential connections between vaccine efficacy and nAAb levels. We were also interested in the impact of immunomodulatory therapies on vaccine efficacy. Clinical residual samples were used for the assessment of the COVID-19 vaccine-elicited immune response (IR) (n=255), as well as for the investigation of the immunization-associated expansion of the nAAb pool (n=185). In order to study the potential interaction between immunomodulatory therapies and the vaccine-induced IR, untreated, healthy individuals and patients receiving anti-TNFα or anti-IL-17 therapies were compared (n total =45). In-house ELISAs (anticitrate synthase, anti-HSP60 and-70) and commercial ELISAs (anti-SARS-CoV-2 ELISAs IgG, IgA, NeutraLISA and IFN-γ release assay 'IGRA') were applied. We found significant differences in the IR given to different vaccines. Moreover, nAAb levels showed plasticity in response to anti-COVID-19 immunization. We conclude that our findings may support the theorem about the non-specific beneficial 'side effects' of vaccination, including the broadening of the nAAb repertoire. Considering immunomodulation, we suggest that anti-TNFα and anti-IL17 treatments may interfere negatively with MALT-associated IR, manifested as decreased IgA titers; however, the modest sample numbers of the herein presented model might be a limiting factor of reaching a more comprehensive conclusion.

Measles Vaccination and Outbreaks in Croatia from 2001 to 2019; A Comparative Study to Other European Countries.

Due to the current burden of COVID-19 on public health institutions, increased migration and seasonal touristic traveling, there is an increased risk of epidemic outbreaks of measles, mumps and rubella (MMR). The aim of the present study was to analyze the epidemiological data on MMR immunization coverage and the number of measles cases in 2001-2019 in Croatia and a number of European countries. Results revealed a decreasing trend in vaccination in 2001-2019 throughout Europe. However, Croatia and Hungary still have the highest primary and revaccination coverage, compared to other analyzed countries. The highest number of measles cases was in 2017 in Romania. There was no significant correlation between the percentage of primary vaccination and the number of measles cases (r = -0.0528, p = 0.672), but there was a significant negative correlation between the percentage of revaccination and the number of measles cases (r = -0.445, p < 0.0001). In conclusion, the results of the present study emphasize the necessity to perform a full protocol of vaccination to reach appropriate protection from potential epidemic outbreaks. Furthermore, in the light of present migrations, documenting the migrants' flow and facilitating vaccination as needed is of utmost importance to prevent future epidemics.

Dynamic Features of Herd Immunity: Similarities in Age-Specific Anti-Measles Seroprevalence Data between Two Countries of Different Epidemiological History.

(1) Background: Measles immunization gap(s) raise the concern of potential outbreaks. Both Croatia and Hungary are situated in the vicinity of measles-endemic countries. Potentially compromised immunization activities due to the COVID-19 surge is a ground for concern. Our aim was to compare age-stratified seroprevalence results in the cross-border region. (2) Methods: Anti-MMR specific antibody levels (IgG) of 950 anonymous Croatian samples were compared with previous Hungarian results (n > 3500 samples), and former Croatian seroprevalence data (n = 1205). Seropositivity ratios were determined using our self-developed anti-MMR indirect ELISA (Euroimmun IgG ELISA kits were used as control). (3) Results: Measured seropositivity ratios of the Croatian samples were largely overlapping with our earlier published Hungarian data (the lowest seropositivity ratios were measured among individuals of 34-43 years of age with 78% of seropositivity) and are in accordance with earlier published data of Croatian researchers. (4) Conclusion: Although the epidemiological histories of the two countries are different, analogies in age-specific measles susceptibility have been discovered. We suggest that besides the potential coincidence in vaccination ineffectiveness, the inherent biological dynamics of vaccination-based humoral protection might have also contributed to the experienced similarities. Our findings may also serve as a lesson regarding the current anti-COVID-19 vaccination strategy.