Dose Of Vaccine Research Articles

The relationship between the recurrence rate of genital warts and administration of quadrivalent human papilloma virus vaccine in women.

In this cohort study a total of 203 women with genital warts, who were referred to gynecology clinic of Shahid Muftah in Yasuj city between 2019 and 2022, were examined and treated by a gynecologist and trained for injection of three doses of Gardasil vaccine after treatment. Of these, 138 women completed the study. Half of them who received three doses of the Gardasil vaccine, aligned in vaccinated group and the other half served as the unvaccinated group. In the vaccinated group, 8 individuals (11.6 %) experienced recurrence, compared to 15 individuals (21.7 %) in the unvaccinated group (p = 0.11). The overall number of recurrence among all participants was 23 (16.7 %). The average duration of treatment until recurrence was 43.6 ± 24.7 weeks in the vaccinated group and 16.4 ± 16.5 weeks in the unvaccinated group (P ≤ 0.017), underscoring the vaccine's preventive role in the recurrence of genital warts.

Danish parents' vaccination readiness is associated with their children's officially registered vaccination history.

Previous research has shown that parents' vaccination readiness, as measured by the 7C vaccination readiness scale, helps to understand whether and why parents are (not) willing to vaccinate their children. However, there is a lack of research investigating the association between parents' vaccination readiness and their children's actual vaccine uptake. Addressing this gap, we examined how Danish parents' level of vaccination readiness is associated with their child's vaccination status combining survey with official registry data. Specifically, parents residing in Denmark (N=2941, 64% female) completed a survey assessing their level of vaccination readiness with the 7C vaccination readiness scale for parents, trust in different sources of information on vaccination, and certainty about vaccinating their child with the next vaccine in the program. Additionally, official vaccination registry data on various recommended child vaccinations was obtained and matched to the survey data of their parents. Results from logistic regression analyses indicate that parents' readiness to vaccinate their children was substantially associated with completion of children's vaccination doses. More precisely, a one-point increase in parents' vaccination readiness score was associated with a two-fold increase in the likelihood of the child being vaccinated with the three main vaccines in the program. The results also show associations between each of the 7C factors, trust items, and demographic variables with real behavior as well as parents' certainty to vaccinate their children in the future. The findings further substantiate the usefulness of assessing parental vaccination readiness, with potential implications for intervention planning by researchers and policymakers.

Recombinant zoster vaccine and the risk of dementia.

Herpes zoster is a potential risk factor for dementia. The effectiveness of the recombinant zoster vaccine for preventing dementia is uncertain. This retrospective cohort study used de-identified claims data from the Optum Labs Data Warehouse database from January 1, 2017, to December 31, 2022, to determine whether the recombinant zoster vaccine is associated with a reduced risk of dementia. Immunocompetent patients with ≥365days of continuous enrollment were included, with the risk period starting upon age-eligibility for the recombinant zoster vaccination. Cox regression adjusted for time-fixed and time-updated measures every six months was implemented to estimate hazard ratios for dementia. Herpes zoster diagnosis and antiviral therapy were also assessed. There were 4,502,678 individuals (median [IQR] age, 62 [54-71] years; 51% female) included in this study: 206,297 (4.6%) were partially vaccinated, and 460,413 (10.2%) were fully vaccinated. The incidence rate of dementia was 99.1 cases per 10,000 person-years in the fully vaccinated group, 108.2 cases per 10,000 person-years in the partially vaccinated group, and 135.0 cases per 10,000 person-years in the unvaccinated group. After adjustment, vaccination was significantly associated with a decreased risk of dementia for two doses (hazard ratio (HR): 0.68; 95% CI: 0.67-0.70; P<.001) and for one dose (HR 0.89; 95% CI: 0.87-0.92; P<.001). Having a herpes zoster diagnosis before the first vaccination dose was associated with an increased hazard of dementia (HR 1.47; 95% CI: 1.42-1.52; P<.001) compared to those with no diagnosis. Antivirals used to treat zoster infection were protective against dementia (HR 0.42; 95% CI: 0.40-0.44; P<.001). These findings suggest that the recombinant zoster vaccine is associated with a decreased risk of dementia and highlight an additional benefit of vaccination beyond preventing herpes zoster.

A systematic review and meta-analysis of adverse events following measles-containing vaccines in infants less than 12 months of age.

Lowering the age for receiving the first dose of a measles-containing vaccine (MCV1) has been suggested to close the emerging immunity gap in infants. However, tolerability remains one of the main concerns for vaccine-hesitant parents. We conducted a systematic review and meta-analysis of reactogenicity following MCV1 in infants under 12months of age. We searched EMBASE and PubMed in February 2021. The search was updated in February 2024. With exception of case reports, we included all English-written original studies published >1985 that contained frequency measures on adverse events (AEs) within 56days following MCV1 in infants <12months of age. We identified all common AEs and their frequencies and combined these across studies in a meta-analysis. The effect of measles strain and vaccine valency was also evaluated. We included 24 studies for analysis: 18 randomized controlled trials (RCTs), three interventional studies, and three observational studies. Only one RCT was placebo-controlled. Commonly reported AEs were injection site reactions, fever, rash, gastrointestinal symptoms, respiratory tract symptoms, conjunctivitis, and symptoms related to the general condition of the infant. The frequency of any AE was generally <10%; however, the placebo-controlled trial showed no difference between MCV1 and placebo-injected infants. Edmonston B strains and measles-mumps-rubella-varicella vaccine (MMRV) were associated with a higher rate of high fever >39°C. Most AEs occurred in <10% of infants receiving MCV1at <12months of age. The placebo-controlled trial suggested no excess reactogenicity following early MCV. Measles strain and vaccine valency may affect AE risks, but other factors such as socioeconomic status, race, and setting could also explain this finding, as these were not equally distributed between studies. Caution is advised when interpreting findings from studies without a placebo group.

Quantitative and qualitative analysis of seroconversion after one year of vaccination with inactivated SARS-CoV-2 vaccine (CoronaVac®) in healthcare workers: Cross-sectional analytical study.

A descriptive study was carried out with health professionals in Sao Paulo city. Were included individuals vaccinated with 2 doses of the inactivated vaccine. Demographic, clinical and vaccination information was obtained from professionals with or without comorbidities. Two serological assays were used to identify the presence and quantity of anti-Spike IgG in serum samples. 433 healthy healthcare professionals were included and 58.9 % completed the 4 clinical stages of serological assessment. Among adults and elderly people, 25.2 % had chronic diseases (hypertension 50.5 %, diabetes 10 % and obesity 6.5 %). Most individuals have 95 % protection in the first 3 months after the second dose, and 67.68 % protection after 6 months. Total antibodies ranged from 3 to 10 on the reactivity index, and the anti-RBD IgG levels were high. CoronaVac has a 94 % seroconversion rate after 2 doses and can prevent serious cases and outbreaks of the disease, if used on a large scale.

Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial.

Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9months (1+1 co-administration) or YF vaccine administered separately at age 10months (1+1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9months (3+0 separate). Blood samples were collected 28-35days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres≥1:8 were calculated with 95% confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than-10%. Forty-eight, 66, and 98 participants enrolled in 3+0 separate, 1+1 co-administration, and 1+1 separate groups respectively had NA results. Per protocol analysis of the 3+0 separate, 1+1 co-administration, 1+1 separate, and the combined 1+1 separate and 3+0 separate groups found that 81%, 85%, 92%, and 88% of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1+1 co-administration and 1+1 separate groups was -7% (95% CI, -18% to 3%). The difference between 1+1 co-administration and 3+0 separate groups was 4% (95% CI, -10% to 15%). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613.

Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59®.

While it remains impossible to predict the timing of the next influenza pandemic, novel avian influenza A viruses continue to be considered a significant threat. A Phase II study was conducted in healthy adults aged 18-64years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A(H7N9) inactivated vaccine administered 21days apart. Participants were randomized (n=105 in each of Arms 1-3) to receive 3.75μg, 7.5μg or 15μg of hemagglutinin (HA) with MF59® adjuvant, or 15μg of HA unadjuvanted vaccine (n=57, Arm 4). The three MF59 adjuvanted vaccines and the 15μg unadjuvanted vaccine were safe and well-tolerated. Little antibody activity was detected against the A(H7N9) vaccine antigen after the first vaccination across study Arms. After second vaccination, the three adjuvanted Arms showed increases in hemagglutination inhibition (HAI), neutralizing (Neut), and neuraminidase inhibition (NAI) geometric mean titers (GMT), peaking at 21days post second vaccination. The percentage of participants with titer ≥1:40 and seroconversion rates for HAI were 30-43% and 0 for the adjuvanted Arms and the unadjuvanted Arm, respectively. Antibody responses against antigenically drifted A(H7N9) strains A/Shanghai/2/2013 and A/Guangdong/17SF003/2016 showed similar trends. Exploratory linear modeling of HAI and Neut responses post second vaccination revealed significantly lower log antibody titers among older participants (aged 35-49 and 50-64years) compared to participants aged 18-34years after adjusting for study vaccination, BMI, sex, and prior seasonal influenza vaccination. Post second vaccination, participants who received seasonal influenza vaccination in at least one of the two previous seasons had significantly lower log antibody titers than participants who did not. Adjuvanted doses of vaccine provided higher antibody responses, on average, than the 15μg unadjuvanted vaccine. Proportion of participants achieving seroconversion and antibody titers ≥40 remained below 50% in all study Arm.

Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease.

Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.

The Disease and Economic Burden of HBV and HCV in Ethiopia.

As the second most populated country in Africa, Ethiopia needs public health measures to control diseases that impact its population. The goal of this study is to analyse disease burdens of HBV and HCV, while also highlighting their estimated associated costs for the country. A literature review and a Delphi process reflecting input of Ethiopian experts and the National Viral Hepatitis Technical Working Group were used to complement mathematical modelling to estimate HBV and HCV disease and economic burdens. Two scenarios were created for HCV: 2023 base and WHO elimination. For HBV, three scenarios were created: 2023 base, WHO elimination and universal birth dose. Using current country costs, each scenario was also examined through an economic lens. There were an estimated 7.6 million HBV infections in 2023. To impact transmission, a universal birth dose and pregnant women screening program would allow Ethiopia to vaccinate approximately 3.9 million infants annually, with a budget of $4.68 million USD, meeting the WHO prevalence elimination target (≤ 0.1% in ≤ 5-year-olds) by 2043. Ethiopia had an estimated 690,000 HCV infections in 2023. To achieve HCV elimination, the country would need to expand screening and treatment to 74,000 individuals annually with a peak budget of $12 million USD per year until 2032, decreasing to less than $2 million USD in 2035. Ethiopia can begin making steps towards elimination of HBV through expansion of birth dose vaccination. However, larger investments will be needed to scale-up treatment and diagnosis interventions for both diseases.

Impact of the infected population and nonlinear incidence rate on the dynamics of the SIR model

This study proposes a dynamical epidemic model SIR incorporating a nonlinear saturated incidence and nonlinear recovery rates. The model considers the influence of available resources, the ratio of the infected population, and the decrease of interventions on the spread of infectious diseases. The use of a nonlinear incident rate as a monoid-type equation improves the study compared to a constant-type incident rate because the spread of infection is now determined by the force of the illness and the number of infected individuals available to disseminate the infection. The consideration of recovery rate, which includes the minimum and maximum feasible recovery rates and the amount of resources available for treatment, makes the research more advantageous. The conditions for the existence of the equilibria have been established. Furthermore, stability analysis and bifurcation have been carried out using Lyapunov’s direct method, the Routh–Hurwitz criterion, and Dulac’s creation under each set of conditions. A numerical simulation was conducted using MATLAB. As the value of the preventive measure increases, the results indicate a considerable decrease in the infected compartment. In addition, the recovered population is growing as more resources, such as oxygen cylinders, hospital beds, and vaccination doses, become available.

Comparative assessment and effectiveness of rotavirus vaccine among 2 months to 5 years old children with acute gastroenteritis including dysentery

Background: Rotavirus infection is a leading cause of severe gastroenteritis in children under five, contributing significantly to morbidity and mortality worldwide. This study aims to find out impact and effectiveness of Rotavirus vaccine (RV5) among 2 months to 5 years old children with acute gastroenteritis including Dysentery. Methods: This is a Prospective Observational study to find out impact and assessment of ROTAVIRUS VACCINE (RV5) among 2 months to 5 years old children admitted with Acute gastroenteritis including Dysentery in a hospital-based setting in Department of Paediatrics, Government medical college between October 2023 to October 2024. Vaccination information collected from Mamta card / Vaccination card. Results: In this study, we compared the severity of AGE based on dehydration among patient who received complete series of Rotavirus vaccine (RV5) and those who not taken the complete dose followed by χ²=9.84 and p value= 0.007 which is statically significant, which indicate that persons who have taken the complete set of rotavirus vaccine has significant decreases in AGE severity than those who have not taken complete dose of Rotavirus vaccine. AGE with no dehydration is observed more in those who had taken complete dose of vaccine and also AGE with severe dehydration is less in those who had taken complete dose of vaccine. Conclusions: Children who have taken all doses of rotavirus vaccine (RV5) has duration of hospital stay and duration of vomiting and duration of diarrhoea is less compared to those who have not taken complete doses of Rotavirus Vaccine.

Immunogenicity of SARS-CoV-2 Vaccination Schedules Including a Booster Dose in Patients with Systemic Lupus Erythematosus: Data from a Prospective Multicenter Study

Objective: To evaluate the humoral response to and impact of SARS-CoV-2 vaccination in patients with systemic lupus erythematosus in a multicenter cohort design. Methods: Data for this analysis were obtained from the Study of Safety, Effectiveness and Duration of Immunity after Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Inflammatory Diseases (SAFER), a prospective, multicenter, phase IV, real-world study conducted across different regions of Brazil from June/2021 to March/2024. Patients aged &gt;18 years with systemic lupus erythematosus (SLE) who received any one of the SARS-CoV-2 vaccines approved by the Brazilian health regulatory agency (CoronaVac [inactivated SARS-CoV-2 vaccine], ChAdOx-1 [AstraZeneca], or BNT162b2 [Pfizer-BioNTech]) were included. Immunogenicity was assessed in pre- and post-vaccination blood samples, and patients were monitored in person and remotely for the occurrence and severity of COVID-19. Results: Two hundred and thirty-five patients with SLE who had completed their vaccination schedules (two doses + booster dose) were included in this study. Most patients were female (89.3%) and had low disease activity or were in remission (72.4%); the majority were also on some form of immunosuppressive therapy (58.1%). One hundred and sixteen patients received two doses of CoronaVac followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, eighty-seven received two doses of ChAdOx1-S (AstraZeneca) followed by one dose of BNT162b2 (Pfizer-BioNTech) vaccine, and thirty-two received three doses of BNT162b2 (Pfizer-BioNTech) vaccine. Twenty-eight cases of COVID-19, none meeting criteria for severe COVID-19, were recorded in patients with respiratory symptoms after the second dose of a SARS-CoV-2 vaccine. Regarding immunogenicity, an increase in seroconversion rate was observed following consecutive vaccine doses, with no difference between vaccination schedules, reaching 97.57% seropositivity after a booster dose. The geometric mean IgG titers differed between the different vaccination schedules after the first and the second vaccine dose, being lowest for the CoronaVac-based schedule, but titers were similar after the administration of a booster dose. Conclusion: In patients with SLE, SARS-CoV-2 vaccines are immunogenic, inducing a robust humoral response. No severe outcomes associated with death or hospitalization were found in the evaluated patient sample. Complete vaccination schedules including a booster dose induced higher humoral responses than incomplete schedules, especially in patients initially immunized with an inactivated virus vaccine schedule and those with a suboptimal humoral response.

A CASE OF CHICKENPOX INFECTION FOLLOWING COVID-19 VACCINATION

We are in the middle of Coronavirus disease 2019 (COVID-19) pandemic and to take control the disease burden several COVID-19 vaccines have been authorized and approved for distribution worldwide. Pfizer-BioNTech vaccine which is a nucleoside-modified RNA vaccine (BNT162b2 Comirnatry) is one of the most important and effective COVID-19 vaccines. As the number of vaccinated people increases, we see various cutaneous side effects related to vaccination. Delayed local reactions, morbilliform rashes, urticaria are among the most common side effects. Herein, a 38-year-old immunocompetent patient with second time experienced chickenpox infection developed immediately after the second dose of Pfizer-BioNTech vaccine is presented. With this case, we reviewed the fact that chickenpox disease is not supply a life-long immunity in all people, it can be re-triggered by some immune mechanisms related with vaccination.

Optimization of Enterovirus-like Particle Production and Purification Using Design of Experiments

Hand, foot, and mouth disease (HFMD) represents an emerging health concern whose main causative agents are Coxsackievirus A6 (CVA6) and enterovirus A71 (EV71). The lack of a CVA6 vaccine and the rise of new HFMD-causing strains due to the containment of established HFMD-causing viruses necessitates the search for alternative vaccine technologies, including virus-like particle (VLP) vaccine candidates. While studies have demonstrated that production of enterovirus-like particles in various organisms can be achieved by expression of the viral P1 structural proteins and the 3CD protease, optimization based on the interplay between the three most commonly altered infection parameters (multiplicity of infection (MOI), viable cell density at the time of infection (VCD), and the infection period) is often not investigated. To address this challenge, we have performed Design of Experiments (DoE) to optimize the production of CVA6 and EV71 VLPs. Our results indicate that CVA6 VLP production peaks at high MOI, high VCD, and long infection periods. Our subsequent downstream purification processes yielded 38 mg and 158 mg of purified CVA6 and EV71 VLPs from 1 L crude harvest, respectively. This translates into thousands of potential vaccine doses and highlights the economic potential of enterovirus-like particles for vaccine purposes.

ULACNet-301, OPTIMO protocol: optimizing HPV vaccination regimen for cancer prevention in children and adolescents living with HIV

BackgroundPersistent infection with human papillomavirus (HPV) is associated with most cervical and anal cancer cases and a large fraction of other anogenital and oropharyngeal cancers. The prophylactic HPV vaccines are known to prevent HPV infections and HPV-associated disease, although there is evidence of reduced response to the HPV vaccination among individuals living with HIV. Prior studies among individuals without HIV suggest that a single HPV vaccine dose induces humoral immune responses that, while lower than those induced by two or three doses, still confer protection against HPV infection. Current recommendations for HPV vaccine include a single-dose schedule for children 9–14-years-olds without HIV. Although two to three doses are recommended for children living with HIV (CLWH), there is very limited data comparing responses to one vs. 2–3 doses in CLWH.MethodsThe OPTIMO study will compare immune responses to HPV vaccination in CLWH by measuring antibody and memory B cell (Bmem) responses after 1, 2, or 3 doses of the 9-valent HPV (9vHPV) vaccine, Gardasil-9. A comparison group of children without HIV will receive one dose of the vaccine. The durability of the response will be assessed at 24 months after the last dose of a given regimen. The OPTIMO trial will take place among CLWH from low and middle-income country (LMIC) settings in Peru, Brazil, and Haiti.DiscussionPrevious studies of single-dose regimens in individuals without HIV raise questions about whether one dose would suffice for CLWH and, if not, whether two or three doses are needed to provide protection against HPV-related cancers. These questions have operational consequences in LMICs given the barriers to delivering multiple doses, uneven availability, and intermittent shortages of HPV vaccines. In addition, information on HIV status for children and adolescents is rarely available during vaccination campaigns based in schools or public health clinics, so CLWH may receive a single dose despite policy recommendations that they receive two or three. This study will provide evidence on the optimal number of doses needed for CLWH that can inform HPV vaccination campaigns in LMICs, especially those with a higher burden of HIV infection and higher incidence of HPV-related cancers.Trial registrationClinicalTrials.gov NCT04265950.

Safety and immunogenicity of Ad26.COV2.S in adolescents: Phase 2 randomized clinical trial

ABSTRACT We conducted a randomized, Phase 2 trial to assess the safety and humoral immunogenicity of reduced doses/dose volume of the standard dose of Ad26.COV2.S COVID-19 vaccine (5 × 1010 viral particles [vp]) in healthy adolescents aged 12–17 years. Participants were randomly assigned to receive Ad26.COV2.S at reduced dose levels of 0.625 × 1010 (0.5 mL), 1.25 × 1010 (0.5 mL) or 2.5 × 1010 (0.5 mL or low volume 0.25 mL) vp in a 1- or 2-dose (56-day interval) primary schedule. Adolescents who received a 1-dose primary schedule received a 2.5 × 1010 vp booster dose 6 months later. Safety and humoral immunogenicity were assessed up to 6 months post-last vaccination. All regimens were well tolerated, with no safety concerns identified. Local and systemic solicited AEs in adolescents were consistent with the known safety profile in adults. All 1- and 2-dose Ad26.COV2.S primary schedules elicited robust peak Spike-binding antibody responses and virus neutralizing titers against the reference strain, in participants with and without preexisting SARS-CoV-2 immunity. Immune responses were durable for at least 6 months. Spike-binding antibody responses were comparable to those elicited in young adults aged 18–25 years who received a standard dose of Ad26.COV2.S in Phase 3 efficacy studies Reduced doses/dose volume of Ad26.COV2.S had an acceptable safety profile and elicited robust humoral immune responses in adolescents aged 12–17 years. All 1- and 2-dose schedules elicited Spike-binding antibody responses that were comparable to an adult population in whom efficacy has been demonstrated using a higher vaccine dose. (clinicaltrials.gov NCT05007080).

Immunosuppressive Therapy Modifies Anti-Spike IgG Subclasses Distribution After Four Doses of mRNA Vaccination in a Cohort of Kidney Transplant Recipients

Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p &lt; 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p &lt; 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p &lt; 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA &gt; 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs.

Feasibility of implementing viral hepatitis services into a correctional service facility in Cape Town, South Africa.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are estimated to be of the most prevalent infectious diseases in correctional settings worldwide. However, viral hepatitis services have not been routinely integrated into South African correctional facilities. We aimed to assess prevalence of HBV infection and HCV infection among people accessing HIV services and assess the feasibility of viral hepatitis service integration in a South African correctional centre. Voluntarily participating people in a correctional services facility were offered free hepatitis B surface antigen (HBsAg) and anti-HCV point-of-care testing in addition to routine HIV testing and treatment services on a first-come, first-served basis during June 2021-March 2022. Off-site laboratory testing (HBV and HCV molecular testing and non-invasive liver fibrosis staging) and screening for hepatocellular carcinoma informed further management. A general practitioner at the facility managed participants, with virtual support from hepatologists. Data on age and history of injecting was collected and point-of-care and laboratory results were recorded. Data were analysed using descriptive statistics. The median age of the 765 people who participated was 32.5 years (IQR 27.5 - 38.2), with 2.2% (17/765) reporting having ever injected a drug. The sample prevalence was 3.9% (30/765) for HBV infection, 0.5% (3/665) for HCV infection, and 1.2% (9/765) for HIV-HBV coinfection. Thirty people had reactive HBsAg point-of-care tests. Among those with reactive HBsAg point-of-care tests 90.0% (27/30) received work-up, among whom 48.1% (13/27) were monitored, 44.4% (12/27) were placed on treatment and two people were released before a management plan could be finalised. Of those treated 33.3% (4/12) started tenofovir/emtricitabine and 66.7% (8/12) antiretroviral therapy. Of the eligible participants, 27.3% (201/735) received at least one hepatitis B vaccine dose and 26.9% (54/201) received three doses. All three participants who had confirmed HCV infection were started on direct-acting antivirals. Of the two completing treatment one achieved sustained virological response at 12 weeks (SVR12), one person was released before SVR12 was done. One person was lost to follow-up. No clinical adverse events were reported. There was a notable viral hepatitis burden among people in this correctional centre and integration of viral hepatitis services into the existing HIV services was acceptable and feasible. Further efforts to sustain and expand access to viral hepatitis services in South African correctional centres could catalyse national viral hepatitis elimination efforts.

Immune Response and Breakthrough Infection Risk After SARS-CoV-2 Vaccines in Patients with Hemoglobinopathy: A Single Center Experience

Background: Immune system impairment is frequently reported in patients affected by hemoglobinopathies due to various mechanisms, including iron accumulation, antigenic stimulation due to numerous transfusions, chronic hemolysis, and a general hyperinflammatory state. For these reasons, the antigenic immune response after a vaccine risks being ineffective. Methods: We evaluated the anti-spike IgG production after two doses of vaccine for SARS-CoV-2 in patients affected by hemoglobinopathies. Results: All 114 enrolled patients (100%) developed adequate antibody production, with a median value of serum IgG of 2184.4 BAU/mL (IQR 1127.4–3502.9). The amount of antibody was unrelated to any other clinical characteristics evaluated, including transfusion dependence or non-transfusion dependence, age, gender, disease type, ferritin, blood count, spleen status, and therapy with hydroxyurea or iron chelators (in all the cases p &gt; 0.05). Moreover, 47 (41.2%) patients developed breakthrough SARS-CoV-2 infection during the first 2 years of follow-up after vaccination, all with a mildly symptomatic course, without requiring hospitalization or experiencing a significative drop in hemoglobin values, allowing for a slight delay in their transfusion regimen. Conclusion: Vaccination against COVID-19 is safe and effective for patients affected by hemoglobinopathies, ensuring adequate protection from severe infection.

Leukocyte Count in Solid Organ Transplant Recipients After SARS-CoV-2 mRNA Vaccination and Infection

Background: Solid organ transplant (SOT) recipients are at risk of severe COVID-19. Vaccination is an important preventive measure but may have side effects, including decreased leukocyte counts. We aimed to describe the prevalence and relative incidence of decreased leukocyte counts and changes in leukocyte counts before and after SARS-CoV-2 mRNA vaccination and SARS-CoV-2 infection in SOT recipients. Methods: Changes in leukocyte counts from before to after each vaccine dose were investigated using linear mixed models. We determined the prevalence of decreased leukocyte counts before and after each vaccine dose and before and after SARS-CoV-2 infection. Self-controlled case series analysis was used to investigate whether the period after either vaccination or infection was associated with risk of decreased leukocyte count. Results: We included 228 adult kidney, lung, and liver transplant recipients. Prior to the first vaccine dose, the mean leukocyte count was 7.3 × 109 cells/L (95% CI 6.9–7.6). Both the leukocyte counts, and the prevalence of decreased leukocyte counts remained unchanged from before to after vaccination regardless of the number of vaccine doses provided. There was no association between vaccination and decreased leukocyte counts (incidence rate ratio (IRR): 0.6; 95% CI: 0.2–2.1; p = 0.461). In contrast, SARS-CoV-2 infection was associated with increased risk of a decreased leukocyte count (IRR: 7.1; 95% CI: 2.8–18.1; p &lt; 0.001). Conclusions: SARS-CoV-2 mRNA vaccination was not associated with risk of decreased leukocyte count and did not affect the prevalence of decreased leukocyte counts in SOT recipients. In contrast, SARS-CoV-2 infection was associated with a higher risk of a decreased leukocyte count.