Immunogenicity after the first dose of the BNT162b2 mRNA Covid-19 vaccine: real-world evidence from Greek healthcare workers

Real-world data regarding the effectiveness, safety and immunogenicity of the Pfizer-BioNTech BNT162b2 mRNA vaccine are accumulating in the literature, suggesting that this vaccine generates high titres of S1-binding IgG antibodies that exhibit potent virus neutralization capacity. This is the first phase IV immunogenicity study to recruit a large number of Greek healthcare workers (n=425) including 63 previously-infected subjects. We measured titres of neutralizing IgGs against the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2 14 days post-immunization with the first dose, employing the SARS-CoV-2 IgG II Quant assay. A total of 92.24 % of our study cohort received a positive assay outcome and titres varied with age. Post-hoc analysis revealed that although titres did not significantly differ among participants aged 20–49 years, a significant decline was marked in the age group of 50–59 years, which was further accentuated in subjects aged over 60. Antibody titres escalated significantly among the previously-infected, indicating the potential booster effect of the first dose in that group.

Booster and anergic effects of the Covishield vaccine among healthcare workers in South India

Covishield (same as ChAdOx1) vaccine was rolled out in January 2021 against SARS-CoV2 in India. Although studies show good efficacy after two doses, there is limited data on the fate of the elicited antibody responses over time in groups with or without prior exposure to SARS-CoV2. Therefore, in this study we proposed to test naive or previously exposed healthcare workers (HCWs) longitudinally after both doses for anti-SARS-CoV2 spike antibody (ASSA) levels. Serum samples were collected from 205 HCWs at days 14 and 28 after first dose, and at days 14, 28 and 3-months after second dose. ASSA levels were quantitated by ECLIA method. Non-responder rate was 17% (35 of 205) on day 14 and 2% (5 of 205) on day 28 after the first dose. After the second dose, the responder rate was 100%. Non-responder rate was significantly higher among males (p<0.00001) and senior citizens (p=0.008). The second dose boosted a 27-fold increase in the COVID-19 naive (CN) group, but caused a 1.5-fold decline in the previously exposed groups. By three months, the antibody levels declined 3-4-folds in all the groups. In spite of high antibody levels (GM-1007 U per ml) after the second dose, 14% developed mild breakthrough infections (BTI). The booster effect was significantly higher when given 10-14 weeks later. The responder rate for Covishield was 98% after first dose and 100% after second dose. The vaccine elicited a prime-boost effect in CN HCWs and a boost-anergy effect in the previously exposed HCWs. ASSA levels began to decline proportionately by three months.

Booster Effect of a Natural Extract of Polypodium leucotomos (Fernblock®) That Improves the UV Barrier Function and Immune Protection Capability of Sunscreen Formulations

Background: Novel approaches to photoprotection must go beyond classical MED measurements, as discoveries on the effect of UV radiation on skin paints a more complex and multi-pronged scenario with multitude of skin cell types involved. Of these, photoimmunoprotection emerges as a crucial factor that protects against skin cancer and photoaging. A novel immune parameter is enabled by the precise knowledge of the wavelength and dose of solar radiation that induces photoimmunosupression. Natural substances, that can play different roles in photoprotection as antioxidant, immune regulation, and DNA protection as well as its possible ability as sunscreen are the new goals in cosmetic industry.Objective: To analyze the effect of a specific natural extract from Polypodium leucotomos (PLE, Fernblock®), as part of topical sunscreen formulations to protect from photoimmunosuppression, as well as other deleterious biological effects of UV radiation.Methods: The possible sunscreen effect of PLE was analyzed by including 1% (w/w) PLE in four different galenic formulations containing different combinations of UVB and UVA organic and mineral filters. In vitro sun protection factor (SPF), UVA protection factor (UVA-PF), contact hypersensitivity factor (CHS), and human immunoprotection factor (HIF) were estimated following the same protocol as ISO 24443:2012 for in vitro UVA-PF determination.Results: PLE-containing formulations significantly reduced UV radiation reaching to skin. Combination of UVB and UVA filters with PLE increased SPF and UVAPF significantly. PLE also increased UV immune protection, by elevating the contact hypersensitivity factor and the human immunoprotective factor of the sunscreen formulations.Conclusion: This study confirms the double role of PLE in photoprotection. Together to the biological activity shown in previous works, the UV absorption properties of PLE confers a booster effect when it is supplemented in topical sunscreens increasing the protection not only at level of erythema and permanent pigment darkening but also against two photoimmunoprotection factors.

Enrichment of Food With Tannin Extracts Promotes Healthy Changes in the Human Gut Microbiota

Food and food bioactive components are major drivers of modulation of the human gut microbiota. Tannin extracts consist of a mix of bioactive compounds, which are already exploited in the food industry for their chemical and sensorial properties. The aim of our study was to explore the viability of associations between tannin wood extracts of different origin and food as gut microbiota modulators. 16S rRNA amplicon next-generation sequencing (NGS) was used to test the effects on the gut microbiota of tannin extracts from quebracho, chestnut, and tara associated with commercial food products with different composition in macronutrients. The different tannin-enriched and non-enriched foods were submitted to in vitro digestion and fermentation by the gut microbiota of healthy subjects. The profile of the short chain fatty acids (SCFAs) produced by the microbiota was also investigated. The presence of tannin extracts in food promoted an increase of the relative abundance of the genus Akkermansia, recognized as a marker of a healthy gut, and of various members of the Lachnospiraceae and Ruminococcaceae families, involved in SCFA production. The enrichment of foods with tannin extracts had a booster effect on the production of SCFAs, without altering the profile given by the foods alone. These preliminary results suggest a positive modulation of the gut microbiota with potential benefits for human health through the enrichment of foods with tannin extracts.

MEASURES FOR PRESERVING THE WELL – BEING OF LIVESTOCK FROM TUBERCULOSIS OWNED BY PERSONAL AUXILIARY AND PEASANT FARMS

About 80% of cattle are in private hands, mostly 3-4, some have more than ten heads. Individual’s farms are not constantly monitored, and if one is clean, most do not pay attention to cleanliness. When animals were tested for TB, it was found that some of the animals are not vaccinated. When the positive ones are slaughtered, if there are no foci of tuberculosis, there is a dispute and the case goes to court. Due to the fact that main source of income for individuals in village is livestock, we tested 1536 cattle in some settlements of Aktobe, Almaty and Zhambyl oblasts against “Pertussis” after 24 hours (96 hours). Then some of the animals' tumors go down or go away (for 3-4 mm). At slaughter there are no changes characteristic of tuberculosis, and sometimes there are tissues infected with pus. Outbreaks of tuberculosis were found in cattle with tumors greater than 5 mm, and 78.7-95.8% of bulls were found to be infected with Mycobacterium tuberculosis. However, in addition to the special instructions for cattle with a skin tumor of 3-4 mm, under the lashes after 4-7 days, in some villages after 14 days by the method of "booster effect", or after 30 days diluted (1: 2, 5000 TB) tuberculin The sowing test was carried out. If an eyelash tumor grows in size of 4 (++++) crosses or 3 (+++) crosses compared to the grafted eyelashes, and if a skin tumor is 5 mm higher in two allergy tests, they are sent to the slaughter in isolation. It has been proven that such additional methods can differentiate the TB reaction from falsehoods and prevent unwarranted slaughter of many healthy animals. Individual barns were cleaned and disinfected after each test.

Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review

Background. Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB). Objective. To determine the IP associated with LTBI, compared to active TB and individuals not infected by M. tuberculosis published in literature. Methods. We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis, Mycobacterium tuberculosis, cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without M. tuberculosis infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants’ information, diagnostic criteria, IP, detection methods, and biases were collected. Results. We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF-α, CSF3, CSF2, CCL1 [I-309], IL-7, TGF-β1, CCL3 [MIP-1α], sIL-2R, TNF-β, CCL7 [MCP-3], IFN-α, fractalkine, I-TAG, CCL8 [MCP-2], CCL21 [6Ckine], PDGF, IL-22, VEGF-A, LXA4, PGE2, PGF2α, sCD163, sCD14, and 15-Epi-LXA4), five were elevated in LTBI (IL-5, IL-17F, IL-1, CCL20 [MIP-3α], and ICAM-1), and two substances were increased among uninfected individuals (IL-23 and basic FGF). We found high heterogeneity between studies including failure to account for the time/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity. Conclusions. It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO CRD42017073289.

SAT-101 The Booster Effect of Aromatase Inhibitor to Overcome Waning Effect of Recombinant Human Growth Hormone

Aromatase inhibitor (AI) is a drug that blocks the conversion of androgens to estrogens, originally approved by FDA as a treatment of breast cancer in postmenopausal women. In several studies, it has been proposed that AI appears effective to improve the final adult height especially combined with rhGH therapy, by delaying growth plate closure. Patients treated with rhGH showed highest growth rate during the first year of treatment, with an average increase of 8–10 cm per year (often called “catch-up” growth), however, followed by a progressive decrease in growth rate over the next several years, which is called “waning effect” of rhGH. In this report, we would like to introduce 2 cases of short pubertal boys showing booster effect of AI when co-treated with rhGH, to overcome waning effect of rhGH and improve the final adult height. Case 1. A boy at the age of 8 years and 1 month visited out clinic with short stature. His height was 118cm (4%), weight was 19.2kg (0%). His MPH was calculated as 173cm. Bone age was 6.9 years by the TW3 method. Initial laboratory finding showed no other abnormal findings including normal IGF-1 levels, so we diagnosed the patient as idiopathic short stature (ISS), and started rhGH treatment. During the rhGH treatment of 4 years and 9 months, the patient obtained additional 30.7cm growth to 148.7cm (23%). However, the patient showed decreased growth velocity of 2.2 cm in the last 6 months, which was thought to be “waning effect” of rhGH. The patient and his parents wanted to improve his height using AI, and after taking agreement about the drug, we added AI. During the combined treatment of 1 year and 10 months, his height was improved to 164.9cm (32%) with a gain of 16.2cm, and no adverse reaction was observed. Case 2. A 8 years and 2 months-old boy visited out clinic with short stature. His height was 116.3cm (0%) and weight was 22.6kg (14%). There have been no unusual findings in past history and family history. His MPH was calculated as 165.9cm. Bone age was 8.2 years by the TW3 method. He was also diagnosed as ISS, and started rhGH treatment. During 5 years and 1 month of rhGH treatment, the patient obtained additional 33.3cm growth to 149.6cm (17%). However, the patient showed progressive decreased growth velocity of 3.3 cm in the last 6 months, so we added AI treatment, and after the combined treatment of 1 year and 5 months, his height was 161.6cm (23%). After that, his parents wanted to quit AI, so we maintained only rhGH treatment for 7 months, and his final height was checked as 167cm. In our cases, we suggest that the additional use of AI to patients with progressive decreased growth rate during previous years of GH treatment can improve growth velocity again, and increase the final adult height with successful bone age suppression, which has not been reported before. Therefore, AI could be expected as effective booster drug to overcome waning effect of rhGH.