FRI0187 IMMUNOGENICITY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: EFFECT OF BIOLOGIC THERAPY ON THE VACCINAL RESPONSE

Background:Vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV-23) in systemic lupus erythematosus (SLE) provides the prevention of severe respiratory infections in patients receiving immunosuppressive therapy. The importance of this vaccination significantly increases before and during treatment with biologics.Objectives:The aim of the study was to evaluate the immunogenicity of PPV-23 in SLE patients.Methods:The study included 52 patients with SLE, including 44 women and 8 men, aged 19 to 68 years. The duration of the disease varied from 9 months to 39 years. At the time of vaccination 7 patients had high, 10 – moderate, 30 – low activity of the disease according to SLEDAI 2K, and 5 had remission. 50 patients received glucocorticoids (GC) 5-30 mg/day equivalent to prednisone, 39 – hydroxychloroquine (GCH), 29 – cytostatics (CS), 20 – biologics: 10 – rituximab (RTM), 10 – belimumab (BLM). 1 dose (0.5 ml) of PPV23 was administered subcutaneously. During the visits, standard clinical and laboratory tests were performed, and the level of antibodies (Ab) to S.pneumoniae in blood serum was determined (VaccZymeTMPCPIg 2 kits – The Binding Site Ltd, Birmingham, UK).Results:In 1-2 months after the vaccination 78.7% of patients had a significant (more than 2 times compared to baseline) increase in the concentration of Ab to the pneumococcal cell wall polysaccharides. A year after vaccination, 61.5% of patients (“responders”) had a significant increase in the concentration of anti-pneumococcal Ab. 20 (38.5%) of 52 patients were considered “non-responders”. Median concentration of anti-pneumococcal Ab was 67[42.6; 105.8] mg/l at visit 1 (initially), 405[143.5; 468.4] mg/l at visit 2 (in 1-2 months), 166.9[77.5; 377.4] mg/l at visit 3 (in 12 months).There were clear differences in the degree of the vaccinal response depending on the therapy: in 20 patients receiving biologics full vaccinal response was achieved significantly less frequently than in patients who did not receive these drugs (40% and 75%, respectively), p=0.02. There were no obvious differences in the vaccinal response during treatment with RTM and BLM (40% of responders in both groups). The vaccinal response significantly decreased during treatment with biologics in combination with GC+/ - GCH (50% of responders). The lowest vaccinal response was observed in patients receiving biologics in combination with GC and CS + / - GCH (33.3% of responders).The analysis of the degree of the vaccinal response depending on the timing of vaccination and the time of biologics infusion was carried out. In the first group (n=6), vaccination was carried out at the optimal time in accordance with the recommendations of EULAR (2020). In the second group (n=14) vaccination was carried out in suboptimal time: during regular treatment with BLM (n=6), 1 week before the next introduction of RTM (n=2), 3-5 months after the last introduction of RTM (5), 1 week before the next introduction of RTM (n=1), 20 days after the BLM termination (n=1). In the first group with optimal vaccination terms, the number of responders was 66.7%, in the second group with suboptimal terms – 28.6%, p=0.27.Conclusion:Sufficient immunogenicity of PPV-23 was shown in SLE patients receiving immunosuppressive therapy. The negative impact of biologics on the vaccinal response was confirmed, especially if the vaccination was not performed at the optimal time in relation to the infusion of the drug or during monthly administration of BLM. If optimal vaccination terms are maintained during the treatment with or initiation of biologics (6 months after the last administration of RTM and 1 month before the next (or first) administration of RTM, 4 months after the last and 1 month before the next (or first) administration of BLM), the number of responders increases significantly. The lowest vaccinal response was obtained in patients receiving combined immunosuppressive therapy with biologics + GC+CS.Disclosure of Interests:None declared

EFFICACY OF SPECIFIC PREVENTION OF INFLUENZA IN INDIVIDUALS WITH POLYMORPHISMS ARG753GLN OF TLR-2, LEU412PHE OF TLR-3, ASP299GLY OF TLR-4 GENES

The aim: Is to study the efficacy of influenza vaccination for individuals with polymorphism Arg753Gln of TLR-2 gene, Leu412Phe of TLR-3 gene, and Asp299Gly of TLR-4 gene. Materials and methods: 66 people with mutant genotypes and normal distribution of alleles of TLR-2, TLR-3, TLR-4 genes, aged 18-63, were inoculated with anti-influenza vaccine. The genotyping of Arg753Gln polymorphic site of TLR-2, Asp299Gly of TLR-4, and Leu412Phe of TLR-3 gene was carried out by polymerase chain reaction with oligonucleotide primers usage. The immunological efficacy of vaccination was evaluated by seroconversion, seroprotection, and dynamics of mean geometric titers of antibodies. Results: It has been established that individuals with mutant genotypes Arg/Gln of TLR-2, Leu/Phe, Phe/Phe of TLR-3, Asp/Gly of TLR-4 genes have a vaccinal response to administering anti-influenza vaccine at the level of subjects with normal distribution of TLR alleles, as evidenced by the growth in dynamics of mean geometric titers of antibodies to vaccine strains, the level of seroprotection and seroconversion. Clinical and epidemiological efficacy of vaccination in this category of people is characterized by: reduction of ARI cases in the postvaccinal period by 2,0-3,0 times; prevention of pneumonia in all vaccinated subjects; decrease in the frequency of bronchitis by 2,5-3,8 times. Conclusions: Effectiveness of influenza vaccination in individuals with Arg573Gln polymorphism of TLR-2, Leu412Phe of TLR-3, Asp299Gly of TLR-4 genes by immune and clinical epidemiological parameters is determined at the level of vaccinated subjects with normal distribution of TLR-2, TLR-3, TLR-4 alleles. Specific influenza immunization of people with polymorphic modified genotypes of TLR-2, TLR-3, TLR-4 genes can prevent the development of pneumonia and reduce the incidence of bronchitis.

Dietary glucomannan improves the vaccinal response in pigs exposed to aflatoxin B1 or T-2 toxin

The aim of the study was to investigate whether dietary supplementation with yeast-derived glucomannan protects pigs against the deleterious effects that exposure to aflatoxin B1 (AFB1) or T-2 toxin has on the vaccinal immune response and drug-metabolising enzymes. Three doses of pure mycotoxin (AFB1 trial: 482, 968 and 1,912 µg/kg feed; T-2 toxin trial: 593, 1,155 and 2,067 µg/kg feed) with or without dietary glucomannan supplementation (2 g/ kg feed) were tested in weaned pigs for 28 days. At days 4 and 15 pigs were immunised with ovalbumin to study the humoral and cell-mediated antigen-specific immune responses. The effects of AFB1 and T-2 toxin intake alone in pigs have already been published. In all parameters investigated no differences were apparent between animals receiving the unsupplemented control diet or the control diet containing glucomannan. In the AFB1 trial glucomannan decreased the severity of liver lesions in animals exposed to 968 µg/kg feed. Exposure to both AFB1 and T-2 toxin were associated with impaired phase I liver enzyme activities, but glucomannan demonstrated a limited protective effect on these enzymes. With regard to the immune defence system, both toxins modulated the vaccinal immune response; AFB1 impaired specific cellular response and T-2 toxin the specific humoral response. Glucomannan supplementation restored the ovalbumin-specific lymphocyte proliferation that was delayed in pigs exposed to AFB1, regardless of dose. In the T-2 toxin trial glucomannan supplementation restored anti-ovalbumin immunoglobulin G production, which was significantly reduced in pigs exposed to both medium and high doses of the toxin. In conclusion, glucomannan dietary supplementation demonstrated no deleterious effects in control animals and protective effects against AFB1 and T-2 toxin immunotoxicity during a vaccinal protocol.

Antibodies specific to infectious bronchitis in broilers in Ceará state, Brazil

The experiment was carried out to determine the antibody levels to infectious bronchitis virus (IBV) in 1120 broilers of two broiler flocks, both from the same parental flock and free from previous vaccination. Forty chicks of each line were alloted to the control group and the sera were tested by indirect ELISA. The vaccination program consisted on the administration of commercial vaccines against IBV at 10 and 25 days of age. Chicks with low levels of maternal antibodies (Mab) did not show significant titers to the first vaccinal stimulus. They presented a vaccinal response to the second vaccinal stimulus reaching the top around GMT 1100 at 45 days. Chicks with high Mab titers did not show significant titers to the primary and secondary vaccinal stimuli, reaching peak levels of GMT 500 at 45 days. No antibody response was detected after the primary vaccination at day 10. A delayed antibody response was detected after the secondary vaccination on day 25, indicating no previous priming. The maternal antibody titers can interfere on the response to the first and second vaccinal stimulus promoting the neutralization of the first vaccination and a different response to the second one, according to high or low maternal antibodies.

Duration of the immune response in subjects inoculated with antimeningococcal A and C vaccines kept in storage at −20°C and at 4°C: influence of pre-vaccination titres on the vaccinal response

SUMMARYThe antibody titres in 250 subjects, aged 5 to 22 years, who were vaccinated with a mannitol-lyophilized antimeningococcal A + C vaccine, stable only when stored at − 20°C, were followed for two years. As measured by indirect haemagglutination (IHA) and indirect immunofluorescence (IF) techniques, titres for both A and CNeisseria meningitidisantibodies remained high. Two years after vaccination titres of antibodies against type A showed fourfold increase over the initial titres in from 46 % to 100 % of groups of subjects and against type C in from 42 % to 80%.For 130 subjects vaccinated with a new lactose–lyophilized antimeningcoccal A + C vaccine (presumed stable at 4°C) antibody titres were measured up to 16 months after inoculation with this vaccine stored at −20°C and also after storage for several periods at 4°C. Antibody titres in all these subjects had fallen to their initial titres by 16 months.The importance of evaluating the results on subjects showing low initial titres (≤1/8 as measured by IHA) is discussed, as inclusion of high initial titres influences the extent of the response.