Booster Dose Research Articles

Farmworker Mobility and COVID-19 Vaccination Strategies: Yuma County, Arizona, 2021.

Farmworkers, a group of essential workers, experience a disproportionately high burden of COVID-19 due to their living and working conditions. This project characterized farmworker mobility in and around Yuma County, Arizona, to identify opportunities to improve farmworker access to COVID-19 vaccination. We collected qualitative and geospatial data through a series of in-person and virtual focus group discussions, key informant interviews, and intercept interviews with participatory mapping. Participants included farmworkers, employers, and representatives of local institutions who serve or interact with farmworkers. We identified participants through purposive and referential sampling and grouped people by sociodemographic characteristics for interviews. We used qualitative and geospatial analyses to identify common themes and mobility patterns. The team interviewed 136 people from February 26 to April 2, 2021. Common themes emerged about how farmworkers have little or no access to COVID-19 vaccination unless offered at their workplaces or at locations where they congregate at convenient times. Further, farmworkers described how their demanding work schedules, long commute times, and caretaker commitments make it challenging to access vaccination services. Geospatial analyses identified three geographic areas in Yuma County where farmworkers reported living and working that did not have a COVID-19 vaccine clinic within walking distance. Coordination between local public health authorities and key partners, including employers and trusted representatives from local community-based organizations or the Mexican consulate, to offer vaccination at worksites or other locations where farmworkers congregate can help improve access to COVID-19 vaccines and booster doses for this population.

Active immunization with inhibin DNA vaccine promotes spermatogenesis and testicular development in rats

ABSTRACT The objective of the present study was to investigate the potential role of immunization against INH on testicular development, serum reproductive hormone (FSH, LH and T) concentrations, testicular biochemical indexes (GGT, ALP, ACP, LDH, α-neutral glucosidase and carnitine) and testicular cell apoptosis in rats. Forty healthy male rats were randomly divided into four groups (n = 10 per group), and respectively immunized with 0.5 mL of C500/pVAX-asd-IS-L (108 CFU/ mL), C500/pVAX-asd-IS-M (109 CFU/ mL), C500/pVAX-asd-IS-H (1010 CFU/ mL) or C500 (1010 CFU/ mL) (thrice with an interval of 2 weeks). P/N values increased after vaccination and differed (p < 0.05) at 1 week and sharply increased at 2 weeks following the booster vaccination (p < 0.01); P/N values indicated that the immune response was induced and production of anti-INH antibodies in rats; Immunization of INH vaccines enhanced serum concentrations of T and FSH, while reduced LH concentrations (p < 0.05); The testis weight, volume, testis coefficient, epididymal weight, sperm count in the epididymis, and the sperm deformity results indicated that INH gene vaccine immunization could promote testicular development and enhance sperm production rate in rats. After immunization of INH gene vaccines, GGT activity was markedly increased, but ALP, LDH and α-neutral glucosidase activities were observably reduced (p < 0.05). Furthermore, flow cytometry results demonstrated that the apoptosis rate of the testicular cells was extremely increased in the C500/pVAX-asd-IS-M group (p < 0.01). These findings illustrate a functional cross-link between FSH, T, LH and spermatogenic markers via inhibin to maintain spermatogenesis. INH immunization may have a positive effect on spermatogenesis and testicular development in male rats.

COVID-19 Vaccination Coverage and Factors Associated With Vaccine Uptake Among People With HIV

People with HIV (PWH) may be at increased risk for severe outcomes with COVID-19 illness compared with people without HIV. Little is known about COVID-19 vaccination coverage and factors associated with primary series completion among PWH. To evaluate COVID-19 vaccination coverage among PWH and examine sociodemographic, clinical, and community-level factors associated with completion of the primary series and an additional primary dose. This retrospective cohort study used electronic health record data to assess COVID-19 vaccination information from December 14, 2020, through April 30, 2022, from 8 health care organizations of the Vaccine Safety Datalink project in the US. Participants were adults diagnosed with HIV on or before December 14, 2020, enrolled in a participating site. The percentage of PWH with at least 1 dose of COVID-19 vaccine and PWH who completed the COVID-19 vaccine primary series by December 31, 2021, and an additional primary dose by April 30, 2022. Rate ratios (RR) and 95% CIs were estimated using Poisson regression models for factors associated with completing the COVID-19 vaccine primary series and receiving an additional primary dose. Among 22 058 adult PWH (mean [SD] age, 52.1 [13.3] years; 88.8% male), 90.5% completed the primary series by December 31, 2021. Among 18 374 eligible PWH who completed the primary series by August 12, 2021, 15 982 (87.0%) received an additional primary dose, and 4318 (23.5%) received a booster dose by April 30, 2022. Receipt of influenza vaccines in the last 2 years was associated with completion of the primary series (RR, 1.17; 95% CI, 1.15-1.20) and an additional primary dose (RR, 1.61; 95% CI, 1.54-1.69). PWH with uncontrolled viremia (HIV viral load ≥200 copies/mL) (eg, RR, 0.90 [95% CI, 0.85-0.95] for viral load 200-10 000 copies/mL vs undetected or <200 copies/mL for completing the primary series) and Medicaid insurance (eg, RR, 0.89 [95% CI, 0.87-0.90] for completing the primary series) were less likely to be fully vaccinated. By contrast, greater outpatient utilization (eg, RR, 1.07 [95% CI, 1.05-1.09] for ≥7 vs 0 visits for primary series completion) and residence in counties with higher COVID-19 vaccine coverage (eg, RR, 1.06 [95% CI, 1.03-1.08] for fourth vs first quartiles for primary series completion) were associated with primary series and additional dose completion (RRs ranging from 1.01 to 1.21). Findings from this cohort study suggest that, while COVID-19 vaccination coverage was high among PWH, outreach efforts should focus on those who did not complete vaccine series and those who have uncontrolled viremia.

Adverse events following immunization of mRNA-1273 (Moderna) booster vaccine in clerkship students

Two-dose primary vaccine administration was the best strategy to reduce the prevalence and severity of COVID-19. Improved immunity and antibody response to the new variant virus by administering a booster vaccine is needed. Health workers are the main priority for administering the mRNA-1273 (Moderna) booster vaccination in Indonesia. This vaccine has high effectiveness, and safety, however, data and evaluation of adverse events following immunization (AEFI) is required. This study aimed to determine the AEFIs of mRNA-1273 booster vaccination in clinical clerkship students as an early adult age group. The research design was a repeated cross-sectional study using purposive sampling technique. There were 214 subjects who met the requirements. Subject filled out an online questionnaire containing evaluation of AEFIs. The most local AEFIs symptoms were pain at the injection site (79.0%), while the common systemic symptoms were headache, drowsiness, weakness, and fever (37.4%; 26.2%; 9.8%; 9.3%). Most AEFIs were felt within 30 minutes to three days. No respondents required hospitalization, experienced anaphylactic shock, became disabled, or died. The AEFIs did not have a significant relationship with gender, history of allergies, co-morbidities, or history of COVID-19. This information is used as a preventive or educational effort to support implementation vaccine in Indonesia.

Evaluating COVID-19 vaccine effectiveness during pre-Delta, Delta and Omicron dominant periods among pregnant people in the U.S.: Retrospective cohort analysis from a nationally sampled cohort in National COVID Collaborative Cohort (N3C)

ObjectivesTo evaluate the effectiveness of COVID-19 vaccinations (initial and booster) during pre-Delta, Delta and Omicron dominant periods among pregnant people via (1) COVID-19 incident and severe infections among pregnant people...

Association of COVID-19 Vaccination With Changes in Smell and Taste.

Since the introduction of vaccines for severe acute respiratory syndrome coronavirus 2in the United States, there has been significant vaccine hesitancy, in part due to fear of adverse effects. We sought to investigate the rates of smell and taste changes after COVID-19 vaccination compared to other common vaccines. Our study cohort included individuals identified by Current Procedural Terminology code in the TriNetX database receiving the COVID-19 first series, COVID-19 booster, influenza, tetanus, diphtheria, pertussis (TDAP), or pneumococcal vaccines between December 15, 2020, and August 15, 2023. After 1:1 propensity score matching, postvaccination incidence of disturbance of smell and taste was significantly less likely after COVID-19 first series vaccine compared to influenza (odds ratios, OR: 0.27 [95% confidence interval, CI: 0.20-0.36]), TDAP (OR: 0.35 [95% CI: 0.26-0.47]), and pneumococcal vaccines (OR: 0.17 [95% CI: 0.09-0.32]). Similarly, incidence of disturbance of smell and taste was significantly less likely after COVID-19 booster vaccine compared to the influenza (OR: 0.60 [95% CI: 0.48-0.76]), TDAP (OR: 0.63 [95% CI: 0.47-0.85]), and pneumococcal vaccines (OR: 0.44 [95% CI: 0.28-0.68]). This study builds upon the literature demonstrating the safety of COVID-19 vaccination.

Effectiveness against severe COVID-19 of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines in persons aged ≥60 years: Estimates over calendar time and by time since administration during prevalent circulation of different Omicron subvariants, Italy, 2022–2023

Evaluating how a COVID-19 seasonal vaccination program performed might help to plan future campaigns. This study aims to estimate the relative effectiveness (rVE) against severe COVID-19 of a seasonal booster dose over calendar time and by time since administration.We conducted a retrospective cohort analysis among 13,083,855 persons aged ≥60 years who were eligible to receive a seasonal booster at the start of the 2022–2023 vaccination campaign in Italy. We estimated rVE against severe COVID-19 (hospitalization or death) of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines by two-month calendar interval and at different times post-administration. We used multivariable Cox regression models, including vaccination as time-dependent exposure, to estimate adjusted hazard ratios (HR) and rVEs as [(1-HR)X100].The rVE of a seasonal booster decreased from 64.9 % (95%CI: 59.8–69.4) in October-November 2022 to 22.0 % (95 %CI: 15.4–28.0) in April-May 2023, when the majority of vaccinated persons (67 %) had received the booster at least 4–6 months earlier. During the epidemic phase with prevalent circulation of the Omicron BA.5 subvariant, rVE of a seasonal booster received ≤90 days earlier was 83.0 % (95 %CI: 79.1–86.1), compared to 37.4 % (95 %CI: 25.5–47.5) during prevalent circulation of the Omicron XBB subvariant. During the XBB epidemic phase, rVE was estimated at 15.8 % (95 %CI: 9.1–20.1) 181–369 days post-administration of the booster dose. In all the analyses we observed similar trends of rVE between persons aged 60–79 and those ≥80 years, although estimates were somewhat lower for the oldest group.A seasonal booster dose received during the vaccination campaign provided additional protection against severe COVID-19 up to April-May 2023, after which the incidence of severe COVID-19 was much reduced. The results also suggest that the Omicron XBB subvariant might have partly escaped the immunity provided by the seasonal booster targeting the original and Omicron BA.4-5 strains of SARS-CoV-2.

Impact of breakthrough SARS-CoV-2 infections on vaccinated patients with colorectal cancer: A retrospective cohort study.

e15656 Background: Cancer patients are vulnerable to severe SARS-COVID outcomes due to the immunosuppressive effect by both the inherent nature of cancer and its diverse therapeutic interventions. Although COVID-19 vaccines have shown efficacy, their effectiveness appears to decrease among cancer patients. We hypothesize that colorectal cancer (CRC) patients are at a higher risk of breakthrough COVID-19 infection and severe outcomes. Methods: We conducted a retrospective cohort study using TriNetX, a population-based database that sources data from electronic medical records (EHRs) of 61 health care organizations in the US. Using ICD-10 codes, we created two cohorts of patients with COVID-19: with CRC and without CRC. The primary aim was a composite outcome of hospitalization, emergency department (ED) visits, and mortality. Secondary aims of our study included risk of hospitalization, ED visits, critical care admission, intubation, and mortality, individually. We performed propensity score matching (PSM) of 44 variables to control for confounding. Odds ratio (OR) and 95% confidence interval (CI) were used to report associations for the propensity-matched cohorts. Results: In CRC patients, the composite outcome (ED visits, hospitalization, death) was 51.6% with breakthrough infections, higher than 44.3% in matched patients without CRC (aOR = 1.39; [95%CI: 1.17 - 1.53]). CRC patients had a significantly elevated cumulative event probability within 180 days (log-rank test, p &lt; 0.0001). Though mortality and critical care stay were similar, CRC patients had a higher risk of hospitalization (aOR = 1.3; [95%CI: 1.12 – 1.50]) and intubation (aOR = 1.79; [95%CI: 1.06 – 3.03]). In subgroup analysis, CRC patients had a higher composite outcome after 2 doses (aOR = 1.39; [95%CI: 1.17 - 1.53]) and 3 doses (aOR = 1.56; [95%CI: 1.26 - 1.95]). Those with 3 doses faced a higher risk of critical stay (aOR = 1.74; [95%CI: 1.06 – 2.86]). Younger CRC patients (16-64 years) with breakthrough infections were at higher risk of all-cause ED visits (aOR = 2.61; [95%CI: 1.73 - 3.94]). No significant differences were observed based on sex. Conclusions: Our retrospective study provides real-world evidence that CRC patients are at a higher risk of more severe outcomes after breakthrough COVID-19 infections. This may warrant a reevaluation of current preventive measures and the possible need for frequent booster vaccine doses for this patient population. [Table: see text]

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

Humoral response after mRNA COVID-19 primary vaccination and single booster dose in people living with HIV compared to controls: A French nationwide multicenter cohort study—ANRS0001s COV-POPART

BackgroundThis study aimed to compare the humoral responses to mRNA COVID-19 vaccination in people living with HIV (PWH) and HIV-negative individuals. MethodsWe included PWH with an undetectable viral load under ART and HIV-negative participants from the French nationwide ANRS COV-POPART cohort who had received two doses of vaccine as a primary vaccination. We compared humoral response between controls and PWH, stratified by CD4 cell count (<200/mm3 and ≥200/mm3 CD4 cell counts) at 1, 6, and 12 months after primary vaccination. ResultsA total of 1776 participants were included in this analysis, 684 PWH (99% were on ART, median CD4 counts 673 cells/mm3) and 1092 controls. At 1 month, after adjustment on age, sex, and BMI, PWH had lower seroneutralization titers than controls, and PWH with <200 CD4 cell/mm3 had lower anti-Spike SARS-CoV-2 IgG antibodies. Same results were found at 6 months. However, in participants who received a booster dose between 6 and 12 months postprimary vaccination, we did not observe differences between PWH and controls at 12 months. ConclusionPWH had high responses to primary mRNA COVID-19 vaccination. In those who received a booster dose after 6 months, the humoral response at 12 months increased to similar levels to controls, even in those with low CD4 counts at baseline.

Establishment of human post-vaccination SARS-CoV-2 standard reference sera

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. ImportanceThe explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.

COVID-19 vaccination before or during pregnancy results in high, sustained maternal neutralizing activity to SARS-CoV2 wild-type and Delta/Omicron variants of concern, particularly following a booster dose or infection

To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). 98 patients completed primary vaccination pre-pregnancy (29·6%) and antenatally (63·3%), 24·2% of whom had antenatal COVID-19, while 7·1% were unvaccinated (28·6% had antenatal COVID-19). None had severe COVID-19. Pre-pregnancy vaccination resulted in vaccination-to-infection delay of 23·3 weeks, which extended to 45·2 weeks with a booster, compared to 16·9 weeks following antenatal vaccination (p<0·001). Infections occurred at 26·2 weeks gestation in women vaccinated pre-pregnancy compared to 36·2 weeks gestation in those vaccinated during pregnancy (p<0·007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio 14·6, p=0·05) and after pre-pregnancy vaccination without a booster (hazard ratio 10·4, p=0·002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.

Inclisiran: the preclinical discovery and development of a novel therapy for the treatment of atherosclerosis

ABSTRACT Introduction Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of global morbidity and mortality. Lipid lowering therapy (LLT) constitutes the cornerstone of ASCVD prevention and treatment. However, several patients fail to achieve therapeutic goals due to low treatment adherence or limitations of standard-of-care (SoC) LLTs. Inclisiran represents a pivotal low-density lipoprotein cholesterol (LDL-C) lowering agent aiming to address current unmet needs in LLT. It is the first available small interfering RNA (siRNA) LLT, specifically targeting PCSK9 mRNA and leading to post-transcriptional gene silencing (PTGS) of the PCSK9 gene. Areas covered Promising phase III trials revealed an ~ 50% reduction in LDL-C levels with subcutaneous inclisiran administration on days 1 and 90, followed by semiannual booster shots. Coupled with inclisiran’s favorable safety profile, these findings led to its approval by both the EMA and FDA. Herein, the authors highlight the preclinical discovery and development of this agent and provide the reader with their expert perspectives. Expert opinion The evolution of gene-silencing treatments offers new perspectives in therapeutics. Inclisiran appears to have the potential to revolutionize ASCVD prevention and treatment, benefiting millions of patients. Ensuring widespread availability of Inclisiran, as well as managing additional healthcare costs that may arise, should be of paramount importance.

A prospective humoral immune monitoring study of kidney transplant recipients receiving three doses of SARS-CoV-2 mRNA vaccine.

Kidney transplant recipients (KTRs), like other solid organ transplant recipients display a suboptimal response to mRNA vaccines, with only about half achieving seroconversion after two doses. However, the effectiveness of a booster dose, particularly in generating neutralizing antibodies (NAbs), remains poorly understood, as most studies have mainly focused on non-neutralizing antibodies. Here, we have longitudinally assessed the humoral response to the SARS-CoV-2 mRNA vaccine in 40 KTRs over a year, examining changes in both anti-spike IgG and NAbs following a booster dose administered about 5 months post-second dose. We found a significant humoral response increase 5 months post-booster, a stark contrast to the attenuated response observed after the second dose. Of note, nearly a quarter of participants did not achieve protective plasma levels even after the booster dose. We also found that the higher estimated glomerular filtration rate (eGFR) correlated with a more robust humoral response postvaccination. Altogether, these findings underscore the effectiveness of the booster dose in enhancing durable humoral immunity in KTRs, as evidenced by the protective level of NAbs found in 65% of the patients 5 months post- booster, especially those with higher eGFR rates.

The Impact of Time between Booster Doses on Humoral Immune Response in Solid Organ Transplant Recipients Vaccinated with BNT162b2 Vaccines.

As solid organ transplant (SOT) recipients remain at risk of severe outcomes after SARS-CoV-2 infections, vaccination continues to be an important preventive measure. In SOT recipients previously vaccinated with at least three doses of BNT162b2, we investigated humoral responses to BNT162b2 booster doses. Anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin G (IgG) was measured using an in-house ELISA. Linear mixed models were fitted to investigate the change in the geometric mean concentration (GMC) of anti-SARS-CoV-2 RBD IgG after vaccination in participants with intervals of more or less than six months between the last two doses of vaccine. We included 107 SOT recipients vaccinated with a BNT162b2 vaccine. In participants with an interval of more than six months between the last two vaccine doses, we found a 1.34-fold change in GMC per month (95% CI 1.25-1.44), while we found a 1.09-fold change in GMC per month (95% CI 0.89-1.34) in participants with an interval of less than six months between the last two vaccine doses, resulting in a rate ratio of 0.82 (95% CI 0.66 to 1.01, p = 0.063). In conclusion, the administration of identical COVID-19 mRNA vaccine boosters within six months to SOT recipients may result in limited humoral immunogenicity of the last dose.

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariants after mRNA SARS-CoV-2 vaccination in kidney transplant recipients

Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.

A Nasal Vaccine Candidate, Containing Three Antigenic Regions from SARS-CoV-2, to Induce a Broader Response.

A chimeric protein, formed by two fragments of the conserved nucleocapsid (N) and S2 proteins from SARS-CoV-2, was obtained as a recombinant construct in Escherichia coli. The N fragment belongs to the C-terminal domain whereas the S2 fragment spans the fibre structure in the post-fusion conformation of the spike protein. The resultant protein, named S2NDH, was able to form spherical particles of 10 nm, which forms aggregates upon mixture with the CpG ODN-39M. Both preparations were recognized by positive COVID-19 human sera. The S2NDH + ODN-39M formulation administered by the intranasal route resulted highly immunogenic in Balb/c mice. It induced cross-reactive anti-N humoral immunity in both sera and bronchoalveolar fluids, under a Th1 pattern. The cell-mediated immunity (CMI) was also broad, with positive response even against the N protein of SARS-CoV-1. However, neither neutralizing antibodies (NAb) nor CMI against the S2 region were obtained. As alternative, the RBD protein was included in the formulation as inducer of NAb. Upon evaluation in mice by the intranasal route, a clear adjuvant effect was detected for the S2NDH + ODN-39M preparation over RBD. High levels of NAb were induced against SARS-CoV-2 and SARS-CoV-1. The bivalent formulation S2NDH + ODN-39M + RBD, administered by the intranasal route, constitutes an attractive proposal as booster vaccine of sarbecovirus scope.

Avidity maturation of humoral response following primary and booster doses of BNT162b2 mRNA vaccine among nursing home residents and healthcare workers.

Infections, despite vaccination, can be clinically consequential for frail nursing home residents (NHR). Poor vaccine-induced antibody quality may add risk for such subsequent infections and more severe disease. We assessed antibody binding avidity, as a surrogate for antibody quality, among NHR and healthcare workers (HCW). We longitudinally sampled 112 NHR and 52 HCWs who received the BNT162b2 mRNA vaccine after each dose up to the Wuhan-BA.4/5-based Omicron bivalent boosters. We quantified anti-spike, anti-receptor binding domain (RBD), and avidity levels to the ancestral Wuhan, Delta, and Omicron BA.1 & 4/5 strains. The primary vaccination series produced substantial anti-spike and RBD levels which were low in avidity against all strains tested. Antibody avidity progressively increased in the 6-8months that followed. Avidity significantly increased after the 1st booster but not for subsequent boosters. This study underscores the importance of booster vaccination among NHR and HCWs. The 1st booster dose increases avidity, increasing vaccine-induced functional antibody. The higher cross-reactivity of higher avidity antibodies to other SARS-CoV-2 strains should translate to better protection from ever-evolving strains. Higher avidities may help explain how the vaccine's protective effects persist despite waning antibody titers after each vaccine dose.

Booster administration of Tc-99m PMT for delayed static imaging in patients with biliary atresia.

Tc-99m N-pyridoxyl-5-methyl-tryptophan (PMT) hepatobiliary scintigraphy has high diagnostic performance for biliary atresia. Our hospital implements standard Tc-99m PMT administration followed by a 6h static imaging review; booster doses are given in cases requiring 24h delayed scans. This study aimed to evaluate the diagnostic performance of this method. A total of 37 pediatric patients who underwent Tc-99m PMT biliary scintigraphy were classified into the surgically-diagnosed biliary atresia or non-biliary atresia groups. The absence of tracer accumulation in the small bowel was considered a hepatobiliary scintigraphic diagnosis of biliary atresia. The Clopper-Pearson method was used to calculate the 95% confidence intervals (CIs) for determining the diagnostic accuracy, negative predictive value, positive predictive value, sensitivity, and specificity of Tc-99m PMT biliary scintigraphy. Among the 37 patients, 12 were classified into the diagnosis of biliary atresia group. Regarding biliary scintigraphy findings, 16 of 37 patients demonstrated tracer accumulation in the small bowel within 6h of testing. These cases were diagnosed as non-biliary atresia, requiring no further testing or booster administration. In contrast, 21 patients underwent delayed testing requiring booster administration, which revealed 13 without tracer excretion and 11 who were diagnosed with biliary atresia. Among the eight patients with tracer accumulation, only one was diagnosed with biliary atresia. Furthermore, two cases without tracer excretion and seven cases with tracer excretion were clinically diagnosed as non-biliary atresia. The diagnostic performance of our examination was as follows: a diagnostic accuracy of 91.9% (34/37; 95% CIs 78.0-98.3%), sensitivity of 91.6% (11/12; 95% CIs 61.5-99.8%), specificity of 92.0% (23/25; 95% CIs 74.0-99.0%), a positive predictive value of 84.6% (11/13; 95% CIs 54.6-98.0%), and a negative predictive value of 95.8% (23/24; 95% CIs 78.9-99.9%). Our protocol for Tc-99m PMT biliary scintigraphy using tracer booster administration demonstrated reliable diagnostic performance for biliary atresia. Notably, 43% of cases did not require booster administration, indicating that lesser radiation exposure may still yield comparable diagnostic accuracy.

Evaluation of Immune Characteristics and Factors Associated with Immune Response following Hepatitis B Vaccination among Ghanaian Adolescents.

WHO recommends HBV-negative babies in high-prevalence (8%) countries receive anti-HBV vaccination. Ghana initiated mass immunization in 2002, but concerns remain about vaccine effectiveness and long-term protection. We evaluated immune characteristics and factors following hepatitis B vaccination among Ghanaian adolescents who received HBV vaccines. In this longitudinal cross-sectional study, 74 participants were enrolled from the Kumasi Metropolis, Ghana. Sociodemographic and lifestyle characteristics of participants were obtained using a questionnaire. Blood samples were obtained before and after booster administration for anti-HBsAg, IL-6, and IL-10 estimations using ELISA kit (Shanghai Chemical Ltd., China). Anti-HBsAg titers ≥10 mIU/ml were considered protective. Statistical analyses were done using SPSS version 26.0 and R programming language, p < 0.05 was considered statistically significant. We found 100% seroconversion rate, with 25.7% seroprotection rate (anti-HBsAg >10 mIU/ml). Gender (p=0.009), age (p=0.001), and exercising (p=0.044) were significantly associated with seroprotection. Following booster administration, 59.4% were hyporesponders (10 ≤ anti-HBsAg titre ≤99 mIU/ml) whilst 40.6% were good responders (anti-HBsAg titre ≥100 mIU/ml). Exercise (p=0.034) was significantly associated with immune response after booster administration. Moreover, we reported significant positive correlation between cytokines [IL-6 (r = 0.817, p < 0.001) and IL-10 (r = 0.928, p < 0.001)] and anti-HBsAg titre. Approximately two thirds of adolescents vaccinated at birth lack protective levels of antibodies against hepatitis B virus. Booster vaccines could aid in mounting protective levels of anti-HBsAg. Physical exercise was negatively associated with immune response to hepatitis B vaccinations.