Median Titer Research Articles

Comparing Antibody Responses to Homologous vs. Heterologous COVID-19 Vaccination: A Cross-Sectional Analysis in an Urban Bangladeshi Population

Background: Vaccination has played a crucial role in mitigating the spread of COVID-19 and reducing its severe outcomes. While over 90% of Bangladesh’s population has received at least one COVID-19 vaccine dose, the comparative effectiveness of homologous versus heterologous booster strategies, along with the complex interplay of factors within the population, remains understudied. This study aimed to compare antibody responses between these booster approaches. Methods: This cross-sectional study enrolled 723 adults in urban Dhaka who had received COVID-19 booster doses within the last six months. Participants were grouped based on homologous or heterologous booster vaccination. Data were collected through structured household surveys, and 2 mL blood samples were collected for measuring antibody titers. Results: Heterologous booster recipients showed higher median antibody titers (8597.0 U/mL, IQR 5053.0–15,482.3) compared to homologous recipients (6958.0 U/mL, IQR 3974.0–12,728.5). In the adjusted analysis, the type of booster dose had no significant impact on antibody levels. However, the duration since the last booster dose was significantly associated with antibody levels, where each additional month since receiving the booster corresponded to approximately a 15–16% reduction in antibody levels (Adj. coeff: 0.85, 95% CI: 0.81, 0.88; p < 0.001). Participants over 40 years demonstrated higher antibody levels than younger individuals (Adj. coeff: 1.23, 95% CI: 1.07, 1.43; p = 0.005). Sex, BMI, and prior COVID-19 infection showed no significant associations with antibody levels after adjustment. Conclusion: The results underscore the complexity of immune responses across different demographic groups and suggest potential benefits of ongoing heterologous booster strategies in sustaining immunity.

Randomised trial of same vs opposite arm co-administration of inactivated influenza and SARS-CoV-2 mRNA vaccines.

The immunogenicity of current influenza vaccines need improvement. Inactivated influenza and COVID-19 mRNA vaccines can be co-administered but randomized controlled trial data is lacking on whether the two vaccines are more immunogenic if given in the same or opposite arms. Murine studies suggest mRNA vaccines can adjuvant influenza vaccines when co-formulated and delivered together. We randomly assigned 56 adults to receive the Afluria quadrivalent inactivated influenza and Moderna monovalent SARS-CoV-2 XBB.1.5 mRNA vaccines, either in opposite arms or both in the same arm at the same site. The primary endpoint was the difference in median combined serum haemagglutination inhibition titre to the H1, H3 and B-Vic vaccine influenza strains after vaccination. We found no significant difference in haemagglutination inhibition antibody levels between the groups (p = 0.30), with the same arm group having a 1.26-fold higher titre than the opposite arm group. There was no difference in analyses of antibodies to individual influenza strains, nor in nasal or saliva antibody levels. While both binding and neutralising antibody titres against SARS-CoV-2 were not significantly different between groups post-vaccination, there was a higher fold-change in BA.5 and ancestral strain neutralising antibodies in the opposite arm group. Influenza vaccination is equivalently immunogenic if given in same or opposite arms as the SARS-CoV-2 vaccine, but it may be preferable to administer the SARS-CoV-2 vaccine at a different site to influenza vaccines. Australian New Zealand Clinical Trials Registry ACTRN12624000445572. Australian National Health and Medical Research Council and Medical Research Future Fund.

Binding Antibodies Responses to SARS-COV-2 Infection in Hospitalized Patients and Vaccinated Subjects: A Longitudinal Prospective Observational Study

Abstract Background: Prevalence of seropositivity following SARS-CoV-2 infection is vital in evaluating herd immunity. However, depending on illness severity, it remains unclear whether the breadth and magnitude of immune response to SARS-CoV-2 infection is for short or long term. Objective: To test the persistence of humoral antibody responses after SARS-CoV-2 exposure in patients with different illness severity and among volunteers who had been vaccinated. Methods: This study was conducted in two Saudi Arabian tertiary hospitals. Participants were categorized as critically ill COVID-19 patients, non-critically ill COVID-19 patients, or vaccinated volunteers. We collected demographic data, COVID-19 exposure history, symptoms, vaccination details, and serum samples to analyze antibody persistence. We evaluated SARS-CoV-2 antibody concentrations in COVID-19 patients with varying disease severity and age groups, as well as in BNT162b2-vaccinated individuals, focusing on IgG levels against the S.FL and S1 domains of the spike protein. Results: The study included 172 adults: 92 unvaccinated hospitalized COVID-19 patients and 80 vaccinated volunteers. All vaccinated subjects demonstrated seropositivity to the SARS-CoV-2 spike protein, with nearly 80% having a median antibody titer of 13,500 AU/mL. Notably, vaccinated subjects exhibited significantly higher IgG levels than naturally infected patients (P < 0.001), including higher S.FL and S1 titers, regardless of severity. Age, comorbidities, and previous infections influenced S-specific antibody levels. Among hospitalized patients, 58% required intensive care, with 28- and 90-day mortality rates of 23% and 43%, respectively. Conclusion: These findings shed light on the immune response dynamics following SARS-CoV-2 infection compared to vaccinated individuals, where the latter showed significantly higher level of antibodies response, providing crucial insights for evaluating short-term herd immunity and the effectiveness of natural infection-induced immunity.

Naturally Acquired Genotype-Specific HPV Seroreactivity and Subsequent HPV Detection Among Heterosexual Partners.

The protective effect of naturally acquired humoral immunity against human papillomavirus (HPV) infection remains unclear. To investigate the role of infection-induced antibodies on HPV detection in heterosexual partners, we used data from 392 unvaccinated couples (females aged 18-25 years attended up to six visits over 2 years; males aged 17-37 years attended up to two visits 4 months apart) enrolled (2005-2011) in Montreal. Genital and blood samples were HPV DNA genotyped and tested for L1 antibody titers of 14 HPV genotypes. Analyses considered female-HPV units (n = 4914 based on 351 couples) and male-HPV units (n = 4214 based on 301 couples); each female and male, respectively, contributed up to 14 observations corresponding to 14 genotypes. Modified Cox and logistic regressions estimated hazard and odds ratios (HR/OR) and 95% confidence intervals (CIs) for genotype-specific HPV detections by partner serostatus (high/low: ≥/< baseline median antibody titers, 392 couples). There were 919 and 231 cumulative HPV detections among female-HPV and male-HPV units, respectively. Risk of HPV detections in females (HR = 1.05, CI: 0.90-1.22) and males (OR = 1.31, CI: 0.97-1.77) was similar between those with partners of high versus low serostatus. Constraining to baseline HPV-negative participants with HPV-positive partners yielded unchanged results. This lack of association suggests that naturally developed HPV antibodies do not protect sexual partners from infection.

Immunogenicity and Safety According to Immunosuppressive Drugs and Different COVID-19 Vaccine Platforms in Immune-Mediated Disease: Data from SAFER Cohort.

The effectiveness of COVID-19 vaccine in patients with immune-mediated inflammatory diseases (IMID) depends on the underlying disease, immunosuppression degree and the vaccine regimens. We evaluate the safety and immunogenicity of different COVID-19 vaccine schedules. The SAFER study: "Safety and effectiveness of the COVID-19 Vaccine in Rheumatic Disease", is a Brazilian multicentric prospective observational phase IV study in the real-life. Data were analyzed after 2 or 3 doses of COVID-19 vaccines: adenoviral vectored vaccine (ChAdOx1 nCoV-19, Astrazeneca), mRNA vaccine (BNT162b2, Pfizer-BioNTech) or inactivated SARS-COV-2 vaccine (CoronaVac, Sinovac Biotech). IgG antibody against SARS-CoV-2 spike (IgG-S) receptor-binding domain level were quantified at baseline (T1) and 28 days after the first (T2), 2nd (T3) and 3rd (T4) doses by chemiluminescence (SARS-CoV-2-IgG-II Quant-assay, Abbott-Laboratories). 721 patients with IMID were included in the analysis. The median titers of IgG-S (BAU/mL) increased progressively over the times: at baseline was 6.26 (5.41-7.24), T2: 73.01 (61.53-86.62), T3: 200.0 (174.36-229.41) and T4: 904.92 (800.49-1022.97). The multivariate linear regression showed that greater IgG-S titers were associated with pre-exposure to COVID-19 (p < 0.001) and BNT162b2 booster vaccine (p < 0.001). Rituximab and immunosuppressant drugs were independent factors for low titers (p = 0.002, p < 0.001, respectively). No serious adverse event was reported. All platforms were safe and induced an increase in IgG-S antibodies. COVID-19 pre-exposure and BNT162b2 booster regimens were predictors of higher humoral immune responses, which is relevant in immunosuppressed populations. Immunosuppressants (mainly rituximab) predicted the lowest antibodies.

Characteristics and outcomes of pediatric brucellosis cases collected from a tertiary academic hospital in Saudi Arabia

Brucellosis is a zoonotic disease caused by Brucella spp., affecting different body systems and leading to multiple complications. Although brucellosis is prevalent in several regions, including Saudi Arabia, limited research has focused on childhood brucellosis. This study aimed to characterize the features and outcomes of brucellosis in pediatric patients. We conducted a retrospective descriptive study involving children (&lt;18 years) with confirmed brucellosis (diagnosed through culture, serology, or both) who received antibiotic therapy. Subjects were stratified into two groups based on age: younger (&amp;le;8 years) and older (&gt;8 years). We assessed treatment outcomes, including clinical cure, mortality, and hospital length of stay. A total of 20 patients were included, with 52.3% in the younger group and 47.7% in the older group. The majority were male (65%), with a mean age of 8.9 years, and 45% required hospitalization. Out of all the patients, only 6 (30%) reported consuming dairy products. Serologically, the baseline median antibody titers for Brucella melitensis and Brucella abortus were 1:1280 and 1:640, respectively. In the younger group, half reported arthralgia and presented with fever. While white blood cell elevation was not significant, C-reactive protein, erythrocyte sedimentation rate, and liver enzymes were elevated at baseline. The administered regimen varied, but about half of the patients received at least three antibiotics. All patients experienced clinical cures, and there were no deaths. This study highlights the characteristics of pediatric brucellosis in a country where the disease is endemic and provides evidence of positive prognosis associated with appropriate antibiotic therapy.

Enhanced RBD-Specific Antibody Responses and SARS-CoV-2-Relevant T-Cell Activity in Healthcare Workers Following Booster Vaccination.

COVID-19 continues to impact healthcare workers (HCWs), making it crucial to investigate vaccine response rates. This study examined HCWs' humoral and cellular immunological responses to COVID-19 booster dosages. We enrolled thirty-four vaccinated HCWs. Twelve received a booster. Post-immunization, the participants' anti-COVID-19 IgG antibodies and IFN-γ secretion were assessed. The median second immunization response time was 406.5 days. Eighteen of twenty-two (81.8%) experienced breakthrough infections after the second vaccination, whereas ten out of twelve individuals who received booster doses had breakthrough infections (83.3%). Six of thirty-four HCWs (17.6%) had no breakthrough infections. Booster-injection recipients had a median antibody titer of 19,592 AU/mL, compared to 7513.55 AU/mL. HCWs with breakthrough infections exhibited a median antibody titer of 13,271.9 AU/mL, compared to 7770.65 AU/mL for those without infections. Breakthrough-infection and booster-injection groups had a slightly higher median T-cell response to antigens 1, 2, and 3. SARS-CoV-2 antibody titer and T-cell responsiveness were positively associated. HCWs sustain cellular and humoral immunity for over 10 months. Irrespective of the type of vaccine, booster injections enhance these immune responses. The results of our research are consistent with previous studies, and a multicenter investigation could validate the findings.

B-046 Development and Validation of an Automated Live Cell-Based Flow Cytometry Assay Platform for Measuring AQP4-IgG

Abstract Background Live cell-based assays (CBA) are considered the gold-standard methodology for detecting pathogenic antibodies targeting neural cell surface antigens. However, the adoption of these methods in clinical laboratories has been limited by their manual nature and low throughput. Here, we describe the development and validation of an automated system utilizing a live flow cytometry-based CBA to detect AQP4-IgG. Establishing AQP4-IgG serostatus is a critical component of the diagnostic criteria for Neuromyelitis optica spectrum disorders (NMOSD) as it enables the differentiation of NMOSD from Multiple Sclerosis where there may be significant clinical overlap. The accurate diagnosis of the correct disease state is vital, as the prognosis and treatment approach differ significantly for these two conditions. Two redundant systems were built that automatically receive reagents (live cells in suspension, buffers, diluents, secondary antibodies, and patients’ samples) and generate flow cytometer ready 96-well plates (each containing up to 45 serum or CSF samples tested in duplicate). Methods We assessed the analytical performance of an AQP4-IgG live flow cytometry-based CBA on these new automated systems. We measured intra- and inter-assay imprecision at three levels in 5x5 format and for end-point titer assessment, accuracy (20 positive and 20 negative sera; 5 positive and 5 negative CSF; established on the current manual assay), reference range (20 negative sera and 20 negative CSF from disease controls), analytical sensitivity (LOB and LOD) and specificity (high IgG containing serum specimens), within-plate draft (1 positive sample near the diagnostic cut-off [IgG-binding index of 2.0] that was tested across the entire plate), instrument to instrument correlation (42 positive samples/dilutions tested simultaneously on both systems), and total throughput for both CSF and Serum. Results Imprecision testing yielded the following results: Serum Intra/Inter precision level 1 (IBI = 2) CV% (current method:4.6%/20.7%), (system 1: 3.1%/18.4%), (system 2: 2.6%/22.5%), serum Intra/Inter precision level 2 (IBI=4) CV% (current method:4.9%/23.3%), (system 1: 3.2%/21.9%), (system 2: 2.6%/24.1%), and serum Intra/Inter precision level 3 (IBI =10) pos CV% (current method:6.0%/31.1%), (system 1: 3.8%/27.4%), (system 2: 4.2%/29.4%), and CSF Intra/Inter precision (IBI =2) CV% (System 1: 11.7%/16.8%), (system 2: 6.1%/10.7%). The median end-point titers for all four samples assessed matched within one end-point titer. For accuracy, 100% qualitative agreement between current and both automated systems, and titration accuracy (5 positive serums, 1 positive CSF) all matched within one titer between current and both automated systems. All reference range samples were negative. LOB/LOD in serum (Current: 0.85/1.11), (System 1: 0.82/0.95), (system 2: 0.82/0.96) and CSF (Current: 1.06/1.52), (System 1: 1.02/1.38), (system 2: 1.02/1.64) were comparable. All high IgG samples were negative. Plate drift analysis showed improved whole plate %CV: (Current:6.52%), (system 1: 4.51%), (system 2: 3.46%). Instrument to instrument comparison utilizing linear regression indicated strong agreement across the two systems (slope = 0.93 and R2= 0.95). Assessment of throughput based on real-time timings indicated a maximum output of approximately &amp;gt;700 patient samples per 24hrs per system. Conclusions An automated system for performing live CBAs provides equivalent to superior analytical performance compared to pre-existing manual methods with improved testing capacity.

Efficacy and Safety of SARS-COV-2 Vaccines in Breast Cancer Patients

Abstract Background Breast cancer (BC) is a major public health problem. COVID-19 pandemic impacted all areas of daily life, including medical care. In particular, delivering care for patients with cancer or suspected cancer during the crisis was challenging given the competing risks of death from untreated cancer versus serious complications from SARS- CoV-2, and the likely higher lethality of COVID-19 in immunocompromised patients. Aim of the Work This study aims to assess the efficacy and immunogenicity of SARS COV 2 vaccines in breast cancer patients by evaluating anti spike antibodies in vaccinated and non vaccinated patients and also through assessing the infection with covid after vaccination (in vaccinated patients) and in non vaccinated patients. The study also aims to assess the Safety of SARS COV 2 vaccine in breast Cancer patients (local and systemic Toxicity). Patients and Methods Our population consisted of 120 female patients diagnosed with early and locally advanced breast cancer, in the breast cancer unit, Clinical oncology department, Ain Shams University Hospitals. All on systemic therapy (on neoadjuvant or adjuvant treatment). Sixty vaccinated and 60 unvaccinated against COVID-19. The cutoff value of SARS COV-2 antibody is 50 BAL/mL (&amp;gt;/= 50 seropositive, &amp;lt;50 seronegative) Results Out of 120 patients, Anti-SARS COV-2 Antibody seropositivity was found to be 48 vs. 58 pts (80% vs. 96.7%) in non vaccinated Vs. Vaccinated patients, with a P-value=0.0046), which was statistically significant. The median titre in both groups was found to be 1434.5 vs. 2500, (P = 0.0026). In the 120 patients, 26 patients had covid infection with a significant difference, Non vaccinated Vs. Vaccinated: 21 vs. 5 pts (35% vs. 8.3 %, P = 0.0004). In the sixty vaccinated patients, mild local adverse events were reported such as warmness at site of injection in 17 patients, representing (28.3%) of patients, Pain 11 (18.3%), Swelling 11 (18.3%), Itch 8 (13.3%), and Redness 6 (60%) representing the least adverse event. The patients experienced mild systemic adverse events, the highest incidence was Fatigue 28 (46.7%), then Myalgia/arthralgia 17(28.3%), headache 2 (3.3%),and fever 16 (26.7%). Conclusion Anti SARS COV2 are effective and safe in localized breast cancer patients on systemic therapy.

Re-emergence of Oropouche virus between 2023 and 2024 in Brazil: an observational epidemiological study

Oropouche virus is an arthropod-borne virus that has caused outbreaks of Oropouche fever in central and South America since the 1950s. This study investigates virological factors contributing to the re-emergence of Oropouche fever in Brazil between 2023 and 2024. In this observational epidemiological study, we combined multiple data sources for Oropouche virus infections in Brazil and conducted in-vitro and in-vivo characterisation. We collected serum samples obtained in Manaus City, Amazonas state, Brazil, from patients with acute febrile illnesses aged 18 years or older who tested negative for malaria and samples from people with previous Oropouche virus infection from Coari municipality, Amazonas state, Brazil. Basic clinical and demographic data were collected from the Brazilian Laboratory Environment Management System. We calculated the incidence of Oropouche fever cases with data from the Brazilian Ministry of Health and the 2022 Brazilian population census and conducted age-sex analyses. We used reverse transcription quantitative PCR to test for Oropouche virus RNA in samples and subsequently performed sequencing and phylogenetic analysis of viral isolates. We compared the phenotype of the 2023-24 epidemic isolate (AM0088) with the historical prototype strain BeAn19991 through assessment of titre, plaque number, and plaque size. We used a plaque reduction neutralisation test (PRNT50) to assess the susceptibility of the novel isolate and BeAn19991 isolate to antibody neutralisation, both in serum samples from people previously infected with Oropouche virus and in blood collected from mice that were inoculated with either of the strains. 8639 (81·8%) of 10 557 laboratory-confirmed Oropouche fever cases from Jan 4, 2015, to Aug 10, 2024, occurred in 2024, which is 58·8 times the annual median of 147 cases (IQR 73-325). Oropouche virus infections were reported in all 27 federal units, with 8182 (77·5%) of 10 557 infections occurring in North Brazil. We detected Oropouche virus RNA in ten (11%) of 93 patients with acute febrile illness between Jan 1 and Feb 4, 2024, in Amazonas state. AM0088 had a significantly higher replication at 12 h and 24 h after infection in mammalian cells than the prototype strain. AM0088 had a more virulent phenotype than the prototype in mammalian cells, characterised by earlier plaque formation, between 27% and 65% increase in plaque number, and plaques between 2·4-times and 2·6-times larger. Furthermore, serum collected on May 2 and May 20, 2016, from individuals previously infected with Oropouche virus showed at least a 32-fold reduction in neutralising capacity (ie, median PRNT50 titre of 640 [IQR 320-640] for BeAn19991 vs <20 [ie, below the limit of detection] for AM0088) against the reassortant strain compared with the prototype. These findings provide a comprehensive assessment of Oropouche fever in Brazil and contribute to an improved understanding of the 2023-24 Oropouche virus re-emergence. Our exploratory in-vitro data suggest that the increased incidence might be related to a higher replication efficiency of a new Oropouche virus reassortant for which previous immunity shows lower neutralising capacity. São Paulo Research Foundation, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, and Brazilian National Council for Scientific and Technological Development. For the Portuguese translation of the abstract see Supplementary Materials section.

Efficacy of Anti-Thyroid Medications in Patients with Graves’ Disease

IntroductionGraves’ disease (GD) is an autoimmune disorder characterized by hyperthyroidism due to increased thyroid-stimulating hormone receptor antibodies (TRAb).The treatment of GD often consists of radioactive iodine therapy, anti-thyroid drugs (ATD), or thyroidectomy. Since few studies have collected data on remission rates after treatment with ATD in Saudi Arabia, our study aimed to assess the efficacy and the clinical predictors of GD long-term remission with ATD use.MethodWe conducted a retrospective chart review study of 189 patients with GD treated with ATD between July 2015 and December 2022 at the endocrine clinics in King Abdulaziz Medical City in Riyadh. All GD patients, adults, and adolescents aged 14 years and older who were treated with ATD during the study period and had at least 18 months of follow-up were included in the study. Patients with insufficient follow-up and those who underwent radioactive iodine (RAI) therapy or thyroidectomy as first-line therapy for GD were excluded from the study.ResultsThe study sample consisted of 189 patients, 72% of whom were female. The patients’ median age was 38years (33, 49). A total of 103 patients (54.5%) achieved remission. The median follow-up period for the patients was 22.0 months (9, 36). Patients who achieved remission had lower mean free T4 levels (25.8pmol/l ± 8.93 versus 28.8pmol/l ± 10.82) (P value = 0.038) and lower median TRAb titer (5.1IU/l (2.9, 10.7)) versus (10.5IU/l (4.2, 22.5)) (P value = 0.001) than patients who did not achieve remission. Thirty-five out of 103 patients who achieved remission (34%) relapsed after ATD discontinuation. The patients who relapsed showed higher median thyroid uptake on 99mTc-pertechnetate scan than patients who did not relapse: 10.3% (5.19, 16.81) versus 6.0% (3.09, 12.38), with a P value of 0.03. They also received ATD for a longer period, 40.0 months (29.00, 58.00) versus 25.0 months (19.00, 32.50), with a P value of < 0.0001.ConclusionThe remission of GD was achieved in approximately half of the patients treated with ATD; however, approximately one-third of them relapsed. Lower Free T4 and TRAb levels at diagnosis were associated with remission. Longer ATD use and higher thyroid uptake upon diagnosis were associated with relapse after ATD discontinuation. Future studies are necessary to ascertain the predictors of ATD success in patients with GD.

Humoral immune response as an indicator for protection against Covid-19 after anti-SARS-COV2-booster vaccination in hematological and oncological patients.

Cancer patients are at a higher risk to develop severe COVID-19 symptoms after SARS-CoV-2 infection compared to the general population and regularly show an impaired immune response to SARS-CoV-2 vaccination. In our oncological center, 357 patients with hematological and oncological diseases were monitored for neutralizing antibodies from October 2021 over 12 months. All patients had received three anti-SARS-CoV-2 vaccinations with an mRNA-(Comirnaty/BionTech or Spikevax/Moderna) or a vector vaccine (Vakzevria/AstraZeneca or JCOVDEN/Johnson&Johnson). Neutralizing anti-SARS-CoV-2 IgG antibodies in the patients' sera were detected within 3 months before, 3-10 weeks and 5-7 months after the booster vaccination (third vaccination). 112 patients developed a breakthrough SARS-CoV-2 infection during the observation period. High anti-SARS-Cov-2 antibody levels before infection significantly protected against symptomatic Covid-19 disease (p = .003). The median antibody titer in patients with asymptomatic Covid-19 disease was 2080 BAU/ml (binding antibody units per Milliliter) and 765 BAU/ml in symptomatic patients. 98% of the solid tumor patients reached seroconversion after the booster vaccination in comparison to 79% of the hematological patients. High antibody titers of >2080 BAU/ml after the booster vaccination were detected in 61% of the oncological and 34.8% of the hematological patients. 7-10 months after the booster vaccination, the anti-SARS-CoV-2 antibody titer declined to an average of 849 BAU/ml. Considering the heterogenous humoral immune response of cancer patients observed in this study, an individual vaccination strategy based on regular measurement of anti-SARS-CoV-2 antibody levels should be considered in contrast to fixed vaccination intervals.

Inactivation of Highly Pathogenic Avian Influenza Virus with High-temperature Short Time Continuous Flow Pasteurization and Virus Detection in Bulk Milk Tanks

Infections of dairy cattle with clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) were reported in March 2024 in the U.S. and viable virus was detected at high levels in raw milk from infected cows. This study aimed to determine the potential quantities of infectious HPAIV in raw milk in affected states where herds were confirmed positive by USDA for HPAIV (and therefore were not representative of the entire population), and to confirm that the commonly used continuous flow pasteurization using the FDA approved 72 °C (161°F) for 15 s conditions for high−temperature short time (HTST) processing, will inactivate the virus. Double-blinded raw milk samples from bulk storage tanks from farms (n = 275) were collected in four affected states. Samples were screened for influenza A using quantitative real-time RT-PCR (qrRT-PCR) of which 158 (57.5%) were positive and were subsequently quantified in embryonating chicken eggs. Thirty-nine qrRT-PCR positive samples (24.8%) were positive for infectious virus with a median titer of 3.5 log10 50% egg infectious doses (EID50) per mL. To closely simulate commercial milk pasteurization processing systems, a pilot-scale continuous flow pasteurizer was used to evaluate HPAIV inactivation in artificially contaminated raw milk using the most common legal conditions in the US: 72 °C (161°F) for 15 s. Among all replicates at two flow rates (n = 5 at 0.5 L/min; n = 4 at 1 L/min), no viable virus was detected. A mean reduction of ≥5.8 ± 0.2 log10 EID50/mL occurred during the heating phase where the milk is brought to 72.5 °C before the holding tube. Estimates from heat-transfer analysis support that standard U.S. continuous flow HTST pasteurization parameters will inactivate >12 log10 EID50/mL of HPAIV, which is ∼9 log10 EID50/mL greater than the median quantity of infectious virus detected in raw milk from bulk storage tank samples. These findings demonstrate that the US milk supply is safe when pasteurized.

Evaluation of cross-neutralizing immunity following COVID-19 primary series vaccination during the Omicron surge in Tanzania.

COVID-19 vaccine became available in Tanzania during the first wave of the Omicron variant. During that time community seroprevalence of SARS-CoV-2 was already at 50%-80%. To date, it remains largely unknown whether ongoing vaccination with the primary series vaccines has any meaningful immune-boosting effects against newer Omicron subvariants. Therefore, we tested cross-neutralizing capacity of antibodies elicited by infection, vaccination, or both against SARS-CoV-2 Omicron subvariants BA.1, and the newer subvariants BQ.1.1 and XBB.1.5. that were unexperienced by this population. Participants who were either SARS-CoV-2 infected-only (n = 28), infected vaccinated (n = 22), or vaccinated-only (n = 73) were recruited from Dar-es-Salaam, Tanzania, between April and December 2022. Plasma 50% neutralization titers (NT50) against SARS-CoV-2 wild-type strain and Omicron subvariants were quantified by a lentiviral-based pseudo-virus assay. Percentage of participants with neutralizing activity against WT and BA.1 was high (>85%) but was reduced against BQ.1.1 (64%-77%) and XBB.1.5 (35%-68%) subvariants. The low median cross-neutralization titer was slightly higher in the infected vaccinated group compared to vaccine-only group against BQ.1.1 (NT50 148 vs. 85, p = 0.032) and XBB.1.5 (NT50 85 vs. 37 p = 0.022) subvariants. In contrast, vaccine-boost among the infected vaccinated did not result to increased cross-neutralization compared to infected-only participants (BQ.1.1 [NT50 of 148 vs. 100, p = 0.501] and XBB.1.5 [NT50 86 vs. 45, p = 0.474]). We report severely attenuated neutralization titers against BQ.1.1 and XBB.1.5 subvariants among vaccinated participants, which marginally improved in the infected vaccinated participants. Our findings call for further studies to evaluate effectiveness of the primary series vaccines in preventing severe infection and mortality against the newer variants.

Antibody responses post-booster COVID-19 vaccination: Insights from a single-center prospective cohort study

The study aimed to evaluate the effect of booster dose COVID-19 vaccines on prevention and humoral immune response in individuals with different vaccination schemes during the period BA.4 and BA.5 omicron sub-variants were globally dominant. The study included 146 individuals who preferred different vaccination schemes for booster doses. Anti-spike/RBD-IgG and neutralizing antibody levels were measured 28 days after the booster dose vaccination upon their consent. There is no significant difference between median antibody titers detected according to different vaccination schemes. SARS-CoV-2 neutralizing antibody inhibition percentages were detected significantly higher in serum samples before and after the last booster dose in 2 BNT162b2+1 BNT162b2(99.42 %), 2 BNT162b2 + 2 BNT162b2(99.42 %), and 2 BNT162b2 + 3 BNT162b2(99.42 %) vaccination schemes (p = 0.004, p = 0.044, p = 0.002,respectively). The study indicated that a booster vaccination dose provides a high level of protection against severe COVID-19 and death. We think that the variant-specific pancoronavirus vaccines will be necessary to protect against breakthrough infections.

Effect of Rabies Booster Vaccination on Antibody Levels in African Wild Dogs (Lycaon pictus).

Rabies is a highly virulent viral disease that has been associated with large-scale population declines of the endangered African wild dog (Lycaon pictus). Rabies vaccination may be a valuable conservation tool in this species, but studies indicate that a single dose does not always confer protective immunity. We examined 47 serum samples from 22 captive African wild dogs (sampled opportunistically for other purposes) to assess whether serum antibody levels after vaccination correlated with the number of doses received and whether other factors affected outcomes. Results of the fluorescent antibody virus neutralization test showed that median antibody titers were 0.085 IU/mL prevaccination, 0.660 IU/mL after a single vaccination, and 22.150 IU/mL after a booster vaccination. Antibody titers above 0.5 IU/mL, internationally accepted as the threshold for seroconversion, were found in none of the samples taken prevaccination, 66.67% of samples taken after primary vaccination, and 90.90% of samples collected after booster vaccination. This study illustrates the probable protective benefit a rabies booster vaccination may provide in African wild dogs and serves as a basis for future research to improve vaccination protocols contributing to the conservation of this endangered species.

Seroprevalence of Bovine Viral Diarrhea Virus in Wild Pigs (Sus scrofa) in 17 States in the USA.

Wild pigs (Sus scrofa) are among the most detrimental invasive species in the USA. They are damaging to crops and agriculture, pose a public health risk as reservoirs of zoonotic pathogens, and may also spread disease to livestock. One pathogen identified in wild pigs is bovine viral diarrhea virus (BVDV), a virus that causes an economically important disease of cattle (Bos taurus and Bos indicus). We sought to determine the BVDV seroprevalence in wild pigs in 17 states across the US and to determine whether age category, sex, or location were associated with a positive antibody titer. Serum samples from 945 wild pigs were collected from 17 US states. Virus neutralization assays were performed to determine antibody titers against BVDV-1b and BVDV-2a. Total BVDV seroprevalence for the study area was 5.8% (95% confidence interval [CI], 4.11-8.89). Seroprevalence across all evaluated states was determined to be 4.4% (95% CI, 2.48-6.82) for BVDV-1b and 3.6% (95% CI, 1.54-5.60) for BVDV-2a. The seroprevalence for individual states varied from 0% to 16.7%. There was no statistical difference in median antibody titer for BVDV-1b or BVDV-2a by sex or age category. State seroprevalences for both BVDV-1b and BVDV-2a were associated with wild pig population estimates for those states.

Immunogenicity of 4-dose Essen intramuscular regimen for rabies post-exposure prophylaxis: A multi-center cross-sectional study in China

BackgroundThe 4-dose Essen intramuscular (IM) regimen for rabies post-exposure prophylaxis (PEP) has been recommended by Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO), but the large-sample clinical evidence is still limited. MethodRabies virus neutralizing antibodies of 11,752 patients were detected from 409 rabies prevention clinics in 27 provinces in China. Patients with serum collected before or no later than 1 h after injection on the day of the fifth dose (day 28) of 5-dose Essen regimen were included in Group A to observe the immune efficacy of 4-dose Essen IM regimen, and patients with serum collected 14–28 days after injection of the fifth dose were included in Group B to observe the immune efficacy of 5-dose Essen IM regimen. ResultsFinally, 2351 cases met the inclusion and exclusion criteria, including 2244 cases in Group A and 107 cases in Group B. The antibody titer of Group A was higher than that of Group B [12.21 (4.15, 32.10) IU/ml vs. 9.41 (3.87, 27.38) IU/ml] (P = 0.002). In Group A, the median antibody titers were 4.01IU/ml, 11.63IU/ml and 29.46IU/ml in patients vaccinated with purified hamster kidney cell vaccine (PHKCV), purified Vero cell vaccine (PVRV), and human diploid cell rabies vaccine (HDCV), respectively, with statistical significance (P < 0.001). ConclusionsThe 4-dose Essen IM regimen could provide satisfactory immune effect, and HDCV induced higher antibody titer than PHKCV or PVRV.

High SARS-CoV-2 infection rate in children unvaccinated with COVID-19 vaccine in Changzhou, China, shortly after lifting zero-COVID-19 policy in December 2022

BackgroundChina experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy.MethodsFrom February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China).ResultsOf the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively.ConclusionVast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.

Heterogeneity and Hierarchy of Immune Response to Primary Immunization in HIV-Infected Children on HAART and the Impact of an Additional Dose of Vaccine.

The nature of vaccine response inferiority is not well studied in children living with HIV (CLHIV). The authors investigated Hepatitis B Virus (HBV) and Diphtheria/Pertussis/Tetanus toxoid (DPT) vaccination responses following primary immunization in CLHIV (n = 42) and healthy controls (HC) (n = 38) and the effect of an additional vaccine dose. Antibody responses, CD4 and HBV-specific T/B cells were analysed using CMIA/ELISA and flow-cytometry. CLHIV had significantly lower baseline median antibody titres for all vaccines than HC (p <0.02). Differential seroprotection rates observed in CLHIV were, 4.8% for pertussis; 9.5% for HBV; 26.2% for diphtheria and 66.7% for tetanus. WHO staging significantly influenced anti-HBs levels (p = 0.0095). HBsAg-specific CD4+T-cells were significantly higher in CLHIV than HC (p = 0.042). An additional vaccine dose (HBV and Tdap) conferred a higher protection rate for tetanus and diphtheria (p <0.040) in CLHIV. These findings suggest that CLHIV exhibit a hierarchy of vaccine responses affecting antibody levels and protection rate, which was rescued by administering additional vaccine dose.