Pre-vaccination allergy testing with COVID-19 mRNA vaccines predicts tolerance

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy, or with an allergic-like reaction after the first dose remains to be defined. Methods: We studied two cohorts of individuals: one pre-vaccination, the second post-vaccination. Skin testing was performed with COVID-19 mRNA vaccines. Upon negative skin test, a two-step (10%-90%) vaccination protocol was performed. Positive skin tests were confirmed with basophil activation tests (BAT). Vaccine-sensitized patients were offered a five-step induction protocol. Results: We identified 187 patients with high-risk profiles for developing anaphylaxis. In parallel, among 385’926 doses of vaccine, 87 allergic-like reactions were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% in the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced acute asthma exacerbation during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Finally, 13 sensitized patients were successfully vaccinated with a five-step vaccination protocol. Conclusion: A two-step 10%-90%-vaccination protocol can be safely administered upon negative skin testing. Yet, it should be delayed in individuals with poorly controlled asthma. Importantly, mRNA vaccine sensitized individuals may receive a five-step vaccination protocol.

Effectiveness of vaccination against symptomatic and asymptomatic SARS-CoV-2 infection: a systematic review and meta-analysis

OBJECTIVE: To assess the effectiveness of SARS-CoV-2 vaccines in terms of prevention of disease and transmission. The evaluation was narrowed to two mRNA vaccines and two modified adenovirus vectored vaccines. METHODS: A frequentist random effects meta-analysis was carried out after data extraction. Risk of bias of the included studies was assessed using New-Castle-Ottawa Scale. The overall risk of SARS-CoV-2 infection confirmed by real time Polymerase Chain Reaction (PCR) was estimated in partially and fully vaccinated individuals. The effect size was expressed as Relative Risk (RR) and RRR (RR reduction) of SARS-CoV-2 infection after vaccination. Potential sources of heterogeneity were investigated through between-study heterogeneity analysis and subgroup meta-analysis. RESULTS: The systematic review identified 27 studies eligible for the quantitative synthesis. Partially vaccinated individuals presented a RRR=73% (95%CI=59%-83%) for any positive SARS-CoV-2 PCR (RR=0.27) and a RRR=79% (95%CI=30%-93%) for symptomatic SARS-CoV-2 PCR (RR=0.21). Fully vaccinated individuals showed a RRR=94% (95%CI=88%-98%) for any SARS-CoV-2 positive PCR (RR=0.06) compared to unvaccinated. According to the subgroup meta-analysis, full BNT162b2 vaccination protocol achieved a RRR=84%-94% against any SARS-CoV-2 positive PCR and a RRR=68%-84% against symptomatic positive PCR. The RR for any SARS-CoV-2 positive PCR remained higher within elderly groups aged ≥69 years (RR=0.12-0.15) compared to younger individuals (RR=0.05-0.12). The RR against B.1.351 infection approached 0.40 for any positive PCR and 0.36 for symptomatic SARS-COV-2 while the RR of any B.1.1.7 infection was 0.14. CONCLUSION: The current licensed vaccines may be transmission blocking, especially after full vaccination protocol. Given the substantial heterogeneity, results should be interpreted with caution. Subgroups meta-analyses suggested that the risk of any SARS-CoV-2 infection may be higher for non-B.1.1.7 variants and individuals aged ≥69 years. Further data and longer follow-up are required to investigate additional sources of heterogeneity and the effectiveness of SARS-CoV-2 vaccination within population subgroups.

MO853SEROLOGICAL RESPONSE AND FACTORS INVOLVED AFTER A VACCINATION PROTOCOL FOR HEPATITIS B VIRUS IN A HEMODIALYSIS UNIT

Background and Aims The population with chronic kidney disease (CKD) presents an increased risk of infection by hepatitis B virus (HBV). Usually, the protective immunological response rate (considering HBV titer > 10 mIU/mL) is 90–95% after the 4th dose of vaccine; In CKD the immune response is lower and correlates with the degree of CKD. In dialysis, this response is variable, less than 50% with three-dose regimens and higher with four doses. Cardiovascular risk factors have been implicated in the response rate to vaccination. The objective of this work is to analyze the efficacy of the HBV vaccine in hemodialysis patients and to identify cardiovascular factors as predictors of response. Method Retrospective observational study. We evaluated the response to a 4-dose vaccination protocol (0-1-2-6 months), determining the levels of HBVA 3 months after the last dose. Demographic variables (age, sex), associated comorbidity, etiology of CKD, among others, were collected. Statistical analysis with SPSS 25.0. Categorical variables are expressed as percentages and have been compared using the Chi2 test. The quantitative variables are expressed as mean +/- standard deviation and the T-student was used to compare them. Statistical significance for a value of p <0.05. Results 89 patients were included; 68.5% are male, with an average age of 65 years. 85.4% had arterial hypertension, and 39.3 were diabetic, the most frequent cause of CKD being renal vascular disease (20.8%), diabetic nephropathy (26.4%) and interstitial (9%). The immune response to HBV vaccination was 79.2%. When making statistical comparisons between the qualitative variables, we have not observed differences between serological response and DM or sex; We did find a trend towards significance when comparing the serological response with the variable HT and etiology of CKD (polycystic kidney disease), pNS. The comparison of means between quantitative variables when performing the Student's T-test did not show differences for any of the study variables. Conclusion In our center, HBV vaccination on dialysis achieves a response rate of 79.2%. HT may condition the immune response to vaccination in HD patients, although significance was not reached. Hereditary pathology has been the one that has shown the best serological response with respect to the rest of etiologies, perhaps associated with greater residual renal function.

Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol.

A survey of Italian cat owners’ attitudes towards cat vaccination through a web-based questionnaire

Background: Vaccination plays an important role in feline healthcare as it is the most effective measure for prevention against feline infectious diseases. Therefore, it is important to know owners’ opinion towards cats’ vaccination and current veterinary practices in order to advice owners on the use of the correct vaccination protocol. This study aimed to identify factors motivating cat owners’ decisions related to vaccination in Italy. A questionnaire was disseminated online (mainly via social networks) to collect data regarding Italian cat owners’ demographics, information about cats, factors regarding vaccination of cats, and veterinary-owner relationship. Results: The majority (90.7%; n=1,131) of cats were vaccinated and 80% (n=998) had been vaccinated within the last three years. Cats 2-4 years old and origin from a breeder or cat shops had a high significant positive impact on the vaccination within the last three years status of cats. Vaccination before the three year period was significantly associated with the importance of cat’s indoor lifestyle, cats ≥ 5 years old and low annual household. The importance for cost vaccination, low annual household income and jobs of owner not related to healthcare had a significant impact on the unvaccination status of cats. In addition, 85.8% of owners present their cat regularly to veterinary clinics. Veterinarians play a significant role in owners’ decision and they are considered the most useful source of information about vaccination by 97.3% of owners. Conclusions: These results could help veterinarians to acquire a greater compliance from owners and better adapt vaccination protocols.

WHO vaccination protocol can be improved to save more lives

Coronavirus disease 2019 (COVID-19) pandemic, a virus infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has impacted all countries of the world, and the main 2021’s challenge is clearly vaccinating the greater number of persons, in the shortest time span, for a maximal reduction in the number of deaths and in the significant economic impacts. Large-scale vaccination aimed to achieve herd immunity poses many logistic and social difficulties [1], with different vaccine candidates and designs [2,3], and vaccination priorities will determine the evolution of the current COVID-19 pandemic. In this paper we explicitly propose an alternative vaccination protocol that can be more effective than those already being deployed, as the ones in the European Union [4] and in the United States [5]. We report strong evidence based on an epidemiological model for the importance of contact hubs (or superspreaders), having a much larger average number of contacts than in the rest of the population [6-11], on the effectiveness of the vaccination strategy. We show that carefully choosing who will be in the first group to be vaccinated can significantly impact on both health services demand and total death toll, by increasing the overall numbers of lives saved and of hospitalizations. We argue that the approach here considered, which does not coincide with current proposals, and given the current conditions with a lack of basic resources for proper vaccination in several countries, and with a significant reduction in mobility and social isolation restrictions, should be considered by all authorities participating in the design of COVID-19 vaccination with the intent of maximising the number of human lives saved.

OPTIMIZING COVID-19 VACCINE USAGE

ABSTRACTAs the worldwide vaccination, it is imperative to minimize vaccine wastage by effectively using all doses available. Vaccine wastage can occur at multiple points during the vaccination process, but it is mainly because the device dead space and the filling process technique. However, there are no studies discussing the waste volume effect of COVID-19 vaccines in clinical practice. There is an increasing COVID-19 vaccine demand that we estimate up to several billion dual doses. The objective of this study was to assess the number of 0.3mL doses obtained from a multiple-dose vial using 1ml and 3ml syringes with different type of needles replicating the first COVID-19 vaccination protocol.Our results suggest that it is possible to obtain six or seven doses from each vial instead five. We provide evidence to optimize between 20% and 40% additional vaccine doses per vial if the current 5-dose vials are used, making scarce supplies go further.It is our duty, as researchers, to ensure the efficacy and efficiency of the worldwide COVID-19 vaccination process. However, if standard syringes-needles and technique are used, there may not be sufficient volume to draw extra doses from a single vial.

Development of an effective vaccination protocol to produce Salmonella-free layer fock

Salmonella infections are of prime importance in the layer chicken industry and pose a significant public health threat. Production of export quality poultry products requires Salmonella-free certification. We developed and applied a vaccination schedule based on a commercial live attenuated Salmonella enterica serovar Gallinarum biovar Gallinarum (S. Gallinarum) vaccine in a layer flock. A flock of 1000 ISA Brown chickens has vaccinated with a lyophilized fowl typhoid live vaccine at definite time intervals. Isolation of Salmonella spp. in cloacal swabs and detection of serum antibody responses were performed using serum plate agglutination (SPA) test and ELISA. At the time of vaccination (16 weeks (w) of age), 50% of the tested birds carried Salmonella spp. in feces. Following booster immunization at 18 w, 21 w, and then every 12 weeks interval, the shedding of Salmonella decreased significantly over time with 40% at 21 w, 10% at 30 w, and 5% each at 42 and 54 w, and no shedding was detected at 66 and 78 w. Biochemical analysis of 32 Salmonella isolates revealed 15.6% (n=5) Salmonella enterica serovar Gallinarum biovar Pullorum (S. Pullorum), 37.5% (n=12) Salmonella Gallinarum, and 46.9% (n=15) paratyphoid causing Salmonella. Of note, the Salmonella spp. detected after 21 w of age belonged to the paratyphoid group. The decreased shedding of bacteria paralleled with increased antibody responses. The antibody level at vaccination (20% positive rate at 16 w) increased over time with a 50% positive rate at 18 w, 80% at 42 w, 90% at 54 w, and 100% at 66 w and 78 w by serum plate agglutination (SPA) test. Similarly, the serum antibody levels of chickens were also measured using ELISA and were similar to the SPA test. In conclusion, the vaccine schedule developed in this study confirmed a high seroconversion and prevented Salmonella shedding in feces. Therefore, a three-month interval vaccination protocol from the pre-laying stage to the last stage of laying is recommended to prevent Salmonella infections in laying flocks.

Update on adherence to a vaccination protocol for invasive bacterial diseases in HIV patients

HIV+ patients present an increased risk of vaccine-preventable invasive bacterial diseases (IBDs), infections characterized by high lethality and frequency of serious complications. Considering that these patients frequently have to face a complex clinical-care pathway, it has been necessary to design a clear vaccination protocol in order to prevent IBDs and to guarantee adequate patient adherence. In 2013 the Local Health Unit Company of Modena's Public Health Department and the University Hospital of Modena developed a shared vaccination protocol to prevent the most common causes of IBDs: Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type B. The protocol applies to HIV+ patients receiving antiretroviral therapy who have a CD4 + cell count > 200 cells / µL. It provides the following vaccination schedule: administration of PCV13 + MenACWY vaccines; after 15 days administration of MenB + Hib vaccines; after 45 days administration of the MenB vaccine; after at least 60 days, administration of PPSV23 + MenACWY vaccines. The first vaccination counselling is proactively carried out by the Public Health Department healthcare workers and takes place at the Infectious Diseases Division in order to improve patient acceptance and adherence to the protocol. From October 2013 to January 2020, 503 HIV+ patients (378 males and 125 females) were vaccinated. Among these patients, 338 (67.2%) completed the vaccination schedule; 110 (21.9%) interrupted the schedule, 34 (6.7%) have a vaccination schedule currently underway and 21 (4.2%) never started the planned vaccination protocol. Overall, the percentage of patients who have completed the vaccination schedule or have scheduled appointments is 73.9%. The data analysis shows a high adherence to the protocol thanks to the collaboration between public health and infectious disease specialists, which improves the compliance of patients with a complex clinical-care pathway. Key messages HIV patients present an increased risk of IBDs and require a tailor-made vaccination protocol. Collaboration between specialists improves the compliance of patients with a complex clinical-care pathway.