Two-dose Vaccination Research Articles

Immunogenicity of two-dose sinopharm BBIB-CorV vaccine in Morocco: One-year follow-up and neutralizing activity against severe acute respiratory syndrome coronavirus 2 variants of concern.

This study aimed to evaluate the immunogenicity of a two-dose Sinopharm BBIB-CorV (Vero cells) vaccine against SARS-CoV-2, at 28 days, 6 months, and 1-year postvaccination. And assess the capacity of two-dose vaccine recipients to neutralize SARS-CoV-2 strains B.1 (Wuhan/D614G), B.1.1.7 (Alpha), AY.33 (Delta), or BA.5.2.2 (Omicron) variants of concern (VOCs). A prospective matched case-control cohort study was conducted at the Military Hospital of Rabat, Morocco between February 2021 and 2022. Immunogenicity was evaluated by standard Microneutralization (MN) assay against four variants (Wuhan D614G, Alpha, Delta, and Omicron). The overall positive neutralizing rates for vaccine recipients against B.1 D614G were 72.09%, 74.82%, and 75.19% on 28-, 180-, 365- day respectively. The proportion of NAbs targeting the Wuhan D614G, and Alpha variants under the BBIBP-CorV vaccination was high on Day 28- and 6 months postvaccination. The immunogenic response to the newly emerging SARS-CoV-2 variants of concern (VOCs), such as Delta and Omicron was comparatively reduced. As a result, it is recommended that additional boost vaccinations be considered.

Evaluating potential program cost savings with a single-dose HPV vaccination schedule: a modeling study.

There is limited evidence on the magnitude of the potential program cost savings associated with the World Health Organization-endorsed single-dose schedule for the human papillomavirus (HPV) vaccine. The objective of this analysis was to model the delivery and vaccine procurement cost implications of the new schedule. The analysis leveraged primary data during a study evaluating the HPV vaccine delivery costs and operational context in 5 countries (Ethiopia, Guyana, Rwanda, Sri Lanka, and Uganda) implementing a two-dose schedule. To estimate the cost for the single-dose schedule, we adjusted the two-dose schedule cost estimates to account for differences in the frequency of activities, whether activities differed by HPV vaccine dose or session, and differences in relative quantity or storage volume of HPV vaccines delivered. We estimated the cost per dose and cost per adolescent receiving the full (single-dose or two-dose) vaccination schedule in 2019 US dollars from a health system perspective. Modeled results found that cost per dose would increase under a single-dose schedule, whereas cost per adolescent receiving the full schedule would decrease. The financial cost for vaccine procurement and delivery per adolescent receiving the full schedule ranged from $9.64 (Sri Lanka) to $23.43 (Guyana) under a two-dose schedule and decreased to $4.84 and $12.34, respectively, under a single-dose schedule, reflecting savings up to 50%. For economic costs, the range for a single-dose schedule was $7.86 (Rwanda) to $28.53 (Guyana). A single-dose HPV vaccination schedule could provide cost savings to immunization programs and enhance program affordability and sustainability.

The Potential Impact of a Single-Dose HPV Vaccination Schedule on Cervical Cancer Outcomes in Kenya: A Mathematical Modelling and Health Economic Analysis

Background: Human Papillomavirus (HPV) is the primary cause of cervical cancer. Single-dose HPV vaccination can effectively prevent high-risk HPV infection that causes cervical cancer and accelerate progress toward achieving cervical cancer elimination goals. We modelled the potential impact of adopting single-dose HPV vaccination strategies on health and economic outcomes in Kenya, where a two-dose schedule is the current standard. Methods: Using a validated compartmental transmission model of HPV and HIV in Kenya, we evaluated the costs from the payer’s perspective to vaccinate girls by age 10 with either one or two doses and increasing coverage levels (0%, 70%, 77%, 90%). Additionally, we modelled single-dose strategies supplemented with either catch-up vaccination of adolescent girls and young women or vaccination for all by age 10, funded with the first five-years of cost savings of switching from a two- to one-dose schedule. Costs and outcomes were discounted at 3% annually, and incremental cost-effectiveness ratios (ICERs) were calculated per disability-adjusted-life-year (DALY) averted. Results: All one-dose and the two-dose 90% coverage strategies were on the efficiency frontier, dominating the remaining two-dose strategies. The two-dose 90% coverage strategy had a substantially higher ICER (US$6508.80/DALY averted) than the one-dose 90% coverage (US$197.44/DALY averted). Transitioning from a two- to one-dose schedule could result in US$21.4 Million saved over the first five years, which could potentially fund 2.75 million supplemental HPV vaccinations. With this re-investment, all two-dose HPV vaccination scenarios would be dominated. The greatest DALYs were averted with the single-dose HPV vaccination schedule at 90% coverage supplemented with catch-up for 11–24-year-old girls, which had an ICER of US$78.73/DALYs averted. Conclusions: Considering the logistical and cost burdens of a two-dose schedule, a one-dose schedule for girls by age 10 would generate savings that could be leveraged for catch-up vaccination for older girls and accelerate cervical cancer elimination in Kenya.

Preparing for outbreaks of vaccine preventable diseases: why are prisons invisible?

Abstract From 1 March 2023 to 29 February 2024, 30 EU/EEA Member States reported a total of 5 770 cases of measles, 4 864 (84.3%) of which were laboratory-confirmed. Th7e highest number of cases were reported by Romania- at the time of writing, 11,397 confirmed cases, including 12 deaths from 1 January 2023 to 7 April 2024. Measles is a highly infectious disease. The best mitigation is vaccination which is highly effective. Outbreaks in many countries have been driven by decreases in vaccine coverage with a two-dose measles-containing vaccine (MCV), especially evident since the COVID-19 pandemic. In many countries, vulnerable migrant populations, ethnic groups and communities experiencing social deprivation have been over-represented in cases and under-covered by vaccine programmes. We know that prisons contain such populations. Historic seroprevalence studies of prison populations, which themselves are scant, show that prison populations are under-vaccinated. Prisons are a setting that can cause disease amplification. Given these facts, it is perhaps surprising that many countries in Europe cannot provide specific surveillance data on either cases in prisons or vaccine coverage specifically in prison populations. Further, that prisons are not often cited as specific settings for vaccine catch-up programmes in national or regional programmes. This is despite evidence of measles cases and outbreaks historically and currently in several European countries. In the presentation we will ask why this ‘blind spot’ in national and international disease surveillance continues and what Member States could and should do to prevent the risk of mass outbreaks of measles in prisons, causing pressures on justice and health systems and risking wider community outbreaks. Finally, we will reflect on how this experience should alert us to the risk of other infectious diseases going undetected, unprevented, and under-studies in prisons, threatening our collective health security.

Świnka w Polsce w 2022 roku

BackgroundMumps, also known as Sudden parotitis, is a viral disease whose main source of infection is the sick/infected person. It posed a serious public health threat in Poland before the introduction of mandatory vaccination. In 2003, Poland introduced the Immunization Program, which included a two-dose vaccination against mumps as part of the MMR (measles, mumps and rubella) vaccine for all children.ObjectiveThe study aimed to assess the epidemiological situation of mumps in Poland in 2022 compared to previous years, including an analysis of the impact of the COVID-19 pandemic.Material and methodsThe analysis of the epidemiological situation of mumps in Poland in 2022 was based on the interpretation of data published in the annual bulletin: "Infectious Diseases and Poisonings in Poland in 2022" and "Vaccinations in Poland in 2022".ResultsIn 2022, 922 cases of mumps were registered in Poland. This was a 90.5% increase compared to 2021 when 484 cases were recorded. The total incidence was 2.4 per 100,000 residents, 84.6% higher than in 2021. The highest incidence of 3.4 per 100 000 residents was registered in the Mazowieckie voivodeship, and the lowest, as in the previous year, was 1.0/100 000 residents in the Dolnośląskie voivodeship. The highest incidence (12.9/100 000) was recorded in children aged 0-4 and 5-9 (16.1/100 000). The incidence in men (3.0/100 000) was higher than in women (1.9/100 000). In 2022, the number of hospitalizations for mumps in Poland was 20, an increase of 122.2% compared to 2021, when 9 people were hospitalized.ConclusionsThe year 2022 showed an overall upward trend in registered mumps cases. The decrease in the number of mumps cases in 2021 was a result of the ongoing pandemic. The restrictions implemented during the pandemic period contributed to a decrease in the number of cases of various droplet-transmitted diseases, including mumps. Still, the observed number of mumps cases in 2022 remains below levels observed during the pre-pandemic COVID-19 period (2019).

Alice in Wonderland Syndrome in Children With Severe Acute Respiratory Syndrome SARS-CoV-2 Infection: A Case Series of Two Patients in an Italian Hospital

BackgroundAlice in Wonderland syndrome (AIWS) is a disorienting neurological condition that affects human perception to the senses of vision, hearing, touch, and sensation and the phenomenon of time. Herein we report two pediatric cases of AIWS temporally related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case presentationAn eight-year-old-girl without history of migraine or epilepsy experienced some episodes of visual distortions (micropsia, macropsia, and teleopsia) and misperception of sound, sometimes associated with headache. The onset of symptoms began at the occurrence of fever (38°C), during SARS-CoV-2 infection. Another six-year-old girl, with no history of migraine or epilepsy, experienced short-term episodes of visual (metamorphopsia) and color disturbance (chromatopsia), during an otherwise asymptomatic SARS-CoV-2 infection. In both cases, clinical examination was unremarkable; surface electroencephalography showed normal findings, without any correlation between visual phenomena and cortical activity; and brain magnetic resonance was normal. The patients were given symptomatic treatment, consisting of anti-inflammatory drugs on demand. The frequency of episodes decreased progressively following a negative SARS-CoV-2 test, with full remission in a few weeks. At the moment of hospital admission, none of the patients had completed the two-dose vaccination schedule for SARS-CoV-2. ConclusionBased on our clinical experience, we believe SARS-CoV-2 may be responsible for AIWS, in addition to other neurological symptoms more frequently documented in the literature. Pathogenesis is multifactorial and arises from the activation of inflammatory pathways. We therefore suggest also searching for SARS-CoV-2, among other viruses linked with AIWS, in children presenting with visual and/or auditory hallucinations, even as isolated symptoms.

Analysis of antibody dynamics in Chinese children aged 1-3 years after single-dose varicella vaccination: A 42 months prospective study

ABSTRACT In China, children aged 12 months receive only a single dose of the varicella vaccine and the incidence of varicella remains high. This study aims to evaluate the changes in immunity among children aged 1–3 years following a single dose of the varicella vaccine, providing a scientific basis for determining the optimal age for a second vaccination. This prospective cohort study employed glycoprotein enzyme-linked immunosorbent assay (gpELISA) for antibody detection. The changes in IgG antibody levels over time post-vaccination were analyzed using a restricted cubic spline (RCS) fitted binary logistic regression model. Varicella surveillance data were collected from the National Notifiable Disease Reporting System (NNDRS). Following a peak in varicella incidence in 2019, the incidence shifted toward older age groups. The cohort study results revealed a seropositivity rate of 100% in children during the 18 months post-vaccination, which subsequently declined to 71.6% by the 42 months. The geometric mean concentration (GMC) decreased from 307.6mIU/mL to 115.2mIU/mL. Additionally, 14 children contracted varicella during the follow-up period, resulting in a breakthrough rate of 2.85%. RCS analysis indicated that antibody levels fell below the protective threshold 18.69 months post-vaccination, with a non-linear decline in the odds ratio(OR) of maintaining antibody concentrations ≥ 50mIU/mL(p < .001, Pnonlinear ≤ 0.001). This study demonstrates that the long-term protective efficacy of a single dose of the varicella vaccine diminishes over time in children, underscoring the necessity of implementing a two-dose vaccination strategy. The findings provide scientific evidence for determining the optimal timing for administering the second dose of the vaccine.

Inactivated vaccine dosage and serum IgG levels correlate with persistent COVID-19 infections in hematologic malignancy patients during the Omicron Surge in China

PurposeThe essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant.MethodsAdults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed.ResultsIn the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001).ConclusionsIn conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels.

The impact of the implementation of the two-dose varicella vaccine immunization strategy in Quzhou: A retrospective birth cohort study

ABSTRACT Varicella is a vaccine-preventable disease caused by the varicella zoster virus (VZV), but the varicella incidence among children has increased in recent years. This was a retrospective birth cohort study based on the Zhejiang Provincial Immune Information System (ZJIIS) and the China Information System for Disease Control and Prevention (CISDCP) in Quzhou. A total of 1,291 clinically diagnosed varicella cases born from 2009 to 2014 were collected during 2009–2023, which were analyzed the impact of changes in vaccination strategy on the incidence of varicella based on the Cox-proportional hazards model. It was observed that the onset age of varicella shifted to the older age group and later to 9–11 years. After the change to the two-dose varicella vaccination strategy, the population affected by varicella was concentrated among students and received more than one dose of live attenuated varicella vaccine (VarV). Based on the Coxproportional hazards model and adjusting for all covariates, the risk of varicella infection in children decreased after the introduction of the two-dose varicella vaccination strategy (HR = 0.04, 95% CI: 0.03–0.05). Meanwhile, the Kaplan–Meier curves also showed that the hazards were lower after the change in vaccination strategy. It is recommended that two doses of VarV should be included in the national immunization schedule and that full vaccination should be completed approximately four years after the first dose.

Evaluation of the Effect of mRNA and Inactivated SARS-CoV-2 Vaccines on the Levels of Cytokines IL-2, IFN-γ, and Anti-RBD Spike SARS-CoV-2 Antibodies in People Living with HIV (PLHIV).

The safety of the mRNA and inactivated SARS-CoV-2 vaccine has been demonstrated for people living with HIV (PLHIV). However, vaccine studies in PLHIV are limited, and there is a gap in which vaccine type provides the best response in PLHIV. Thus, PLHIV may benefit from mRNA vaccine types compared to inactivated vaccines. This study aims to assess the immune responses to vaccination by measuring specific antibodies (IgG) targeting the receptor binding sites (RBDs) of the SARS-CoV-2 virus and the levels of IL-2 and IFN-γ in plasma. A total of 41 PLHIV who regularly take antiretroviral therapy (ART) over a period of six months, along with 31 individuals in a healthy control group (HC), were administered either two mRNA or inactivated vaccines. Data regarding demographics and clinical information were gathered from the medical records. An analysis was conducted on the neutralisation antibody IgG specific to RBD using the chemiluminescence microparticle assay (CMIA). The levels of IL-2 and IFN-γ were quantified using the Luminex assay method from plasma samples. Data were collected in the laboratory 28 days after each vaccination. After the first vaccination, the level of anti-SARS-CoV-2 RBD IgG was higher in PLHIV who received the mRNA vaccines than those who received inactivated vaccines (p = 0.006). The levels of mRNA in the PLHIV group showed a significant correlation with IL-2 and IFN-γ after the second vaccination (r = 0.51, p = 0.0035; r = 0.68, p = 0.002). The group of PLHIV who received the inactivated vaccine showed increased IL-2 and IFN-γ after the initial vaccination, compared to PLHIV who received the mRNA vaccine (p = 0.04; p = 0.08). Administering a two-dose vaccination is essential to increase the levels of neutralising antibodies significantly (p = 0.013) in PLHIV who have received inactivated vaccines; further study is needed to make this a recommendation. The responses observed after vaccination in PLHIV were not affected by their CD4 cell counts. PLHIV showed higher levels of SARS-CoV-2 IgG and increased IL-2 and IFN-γ levels. Our study encourages SARS-CoV-2 vaccination in PLHIV regardless of its CD4 cell counts. Furthermore, the mRNA vaccine may give robust high antibody responses in PLHIV.

Effectiveness of EV-A71 Vaccine and Its Impact on the Incidence of Hand, Foot and Mouth Disease: A Systematic Review.

Vaccination is a highly effective strategy for the prevention of enterovirus A71 (EV-A71)-hand, foot, and mouth disease (HFMD). Three inactivated EV-A71 vaccines in China have demonstrated remarkable efficacy against EV-A71-HFMD during clinical trials, exhibiting vaccine effectiveness (VE) exceeding 90% and few adverse events (AEs). However, the effectiveness of vaccines in the real world and its impact on the epidemiological characteristics of HFMD after the use of EV-A71 inactivated vaccine are uncertain. The odd ratio (OR) and 95% confidence (CI) were used as the effect estimates of the meta-analysis in the test-negative design (TND), and the OR was used to calculate VE: VE = (1 - OR) × 100%. According to the literature search strategy, a comprehensive search was conducted in PubMed, Web of Science (including Chinese Science Citation Database and MEDLINE), and Embase, and 18 records were ultimately included in this study. Subsequently, the overall VE and 95% CI of different vaccine doses were analyzed, with the one-dose vaccine at 66.9% (95% CI: 45.2-80.0%) and the two-dose vaccine at 84.2% (95% CI: 79.4-87.9%). Additionally, the most reported AEs were mild general reactions without any rare occurrences. Simultaneously, the widespread use of the EV-A71 vaccine would lead to a reduction in both the incidence of EV-A71-associated HFMD and severe cases caused by EV-A71. The administration of the two-dose EV-A71 vaccine is highly effective in preventing HFMD in the real world, and the widespread use of the EV-A71 vaccine leads to a reduction in the incidence of EV-A71-associated HFMD and that of severe cases caused by EV-A71. The findings suggest that administering the two-dose EV-A71 inactivated vaccine to children aged 6 months to 71 months can be effective in preventing EV-A71-associated HFMD, highlighting the need for developing a multivalent HFMD vaccine for preventing cases not caused by EV-A71.

Booster vaccination using bivalent DS-5670a/b is safe and immunogenic against SARS-CoV-2 variants in children aged 5-11 years: a phase 2/3, randomized, active-controlled study.

DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, non-inferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here. Children aged 5-11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29. Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, -7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8-29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off. Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years. https://jrct.niph.go.jp/, identifier jRCT2031220665.

Understanding the change of in-hospital mortality and respiratory failure between Delta and Omicron waves from a tertiary hospital in Southern Thailand: A retrospective cohort study

ObjectivesThis retrospective cohort study aims to assess the incidence and associated factors of in-hospital mortality and respiratory failure among patients with COVID-19 during the Omicron and Delta epidemics. MethodsWe reviewed medical records from a regional hospital in Southern Thailand of patients with COVID-19 during the Delta wave (August 2021 to December 2021) and the Omicron wave (February 2022 to June 2022). A computer-generated random sampling approach was used to select patients for analysis. Logistic regression identified factors associated with respiratory failure, while Cox proportional hazard models were used for in-hospital mortality associations. ResultsAmong 5729 hospitalized patients with COVID-19 (Delta: 1229; Omicron: 4500), 1164 were randomly sampled (Delta: 295; Omicron: 869). Patients during the Delta wave were older (median: 52.0; interquartile range: 31.5-70.0) compared with those during the Omicron wave (median: 37.0; interquartile range: 8.0-65.0), with lower rates of completed two doses of vaccination (Delta: 18.3%; Omicron: 51.8%). The Delta variant exhibited higher rates of respiratory failure (46.8% vs Omicron: 22.3%) and in-hospital mortality (12.5% vs Omicron: 6.9%). Increased age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI] 1.03-1.04), severity at admission (aOR 12.48, 95% CI 7.21-22.22), and delayed time to admission (aOR 1.07, 95% CI 1.02-1.12) increased the risk of respiratory failure, while receiving two-dose vaccination reduced this risk (aOR 0.36, 95% CI 0.24-0.53). Similarly, increased age (adjusted hazard ratio [aHR] 1.05, 95% CI 1.03-1.06), severity at admission (aHR 7.20, 95% CI 4.09-12.60), and delayed time to admission (aHR 1.05, 95% CI 1.00-1.11) were associated with higher in-hospital mortality, with two-dose vaccination decreasing this risk (aHR 0.45, 95% CI 0.27-0.75). ConclusionsThe Delta variant exhibited higher in-hospital mortality and respiratory failure rates compared with Omicron. The identification of high-risk groups emphasizes the critical need for timely care for vulnerable patients. Timely access to care and vaccination coverage are crucial in reducing respiratory failure and mortality due to COVID-19, highlighting the necessity for tailored interventions to mitigate the impact of emerging variants.

Optimal Allocation of Multi-Type Vaccines in a Two-Dose Vaccination Campaign for Epidemic Control: A Case Study of COVID-19

As a typical case of the optimal planning for the provision of restricted medical resources, widespread vaccination is considered an effective and sustainable way to prevent and control large-scale novel coronavirus disease 2019 (COVID-19) outbreaks. However, an initial supply shortage of vaccines is inevitable because of the narrow production and logistical capacity. This work focuses on the multi-type vaccine resource allocation problem in a two-dose vaccination campaign under limited supply. To address this issue, we extended an age-stratified susceptible, exposed, infectious, and recovered (SEIR) epidemiological model to incorporate a two-dose vaccination campaign involving multiple vaccine types to fully characterize the various stages of infection and vaccination. Afterward, we integrated the proposed epidemiological model into a nonlinear programming (NLP) model to determine the optimal allocation strategy under supply capacity and vaccine hesitancy constraints with the goal of minimizing the cumulative number of deaths due to the pandemic over the entire planning horizon. A case study based on real-world data from the initial mass vaccination campaign against COVID-19 in the Midlands, England, was taken to validate the applicability of our model. Then, we performed a comparative study to demonstrate the performance of the proposed method and conducted an extensive sensitivity analysis on critical model parameters. Our results indicate that prioritizing the allocation of vaccines to elderly persons is an effective strategy for reducing COVID-19-related fatalities. Furthermore, we found that vaccination alone will not be sufficient for epidemic control in the short term, and appropriate non-pharmacological interventions are still important for effective viral containment during the initial vaccine rollout. The results also showed that the relative efficacy of the first dose is a vital factor affecting the optimal interval between doses. It is always best to complete the two-dose vaccination schedule as soon as possible when the relative efficacy of the first dose is low. Conversely, delaying the second dose of a vaccine as long as possible to increase the proportion of the population vaccinated with a single dose tends to be more favorable when the relative efficacy of the first dose is high. Finally, our proposed model is general and easily extendable to the study of other infectious disease outbreaks and provides important implications for public health authorities seeking to develop effective vaccine allocation strategies for tackling possible future pandemics.

Varicella-Zoster Virus Pretransplant Vaccination and Posttransplant Infections Among Pediatric Solid Organ Recipients in the Two-Dose Varicella Era: A Single-Center, Multi-Organ Retrospective Study.

Varicella-zoster virus (VZV) pretransplant immunization rates, exposures, and posttransplant disease are poorly characterized among pediatric solid organ transplant (SOT) recipients in the two-dose varicella vaccine era. A retrospective analysis of the electronic health records among children <18 years old who received SOT from January 1, 2011 through December 31, 2021, was performed at a single center to assess for missed pretransplant varicella vaccination opportunities, characterize VZV exposures, and describe posttransplant disease. Among 525 children, 444 were ≥6 months old (m.o.) at SOT with a documented VZV vaccine status. Eighty-five (19%) did not receive VZV Dose One; 30 out of 85 (35%) could have been immunized. Infants 6-11 m.o. accounted for 14 out of 30 (47%) missed opportunities. Among children ≥12 m.o. with documented Dose Two status (n = 383), 72 had missed vaccination opportunities; 57 out of 72 (79%) were children 1-4 years old. Most children had unclassifiable pre-SOT serostatus as varicella serology was either not obtained/documented (n = 171) or the possibility of passive antibodies was not excluded (n = 137). Of those with classified serology (n = 188), 69 were seroimmune. Forty-seven of 525 (9%) children had recorded VZV exposures; two developed varicella-neither had documented pre-SOT seroimmunity nor had received post-exposure prophylaxis. Nine additional children had medically attended disease: four primary varicella and five zoster. Of the 11 cases, 10 had cutaneous lesions without invasive disease; one had multi-dermatomal zoster with transaminitis. Seven (64%) received treatment exclusively outpatient. VZV exposure and disease still occur. Optimizing immunization among eligible candidates and ensuring patients have a defined VZV serostatus pretransplantation remain goals of care.

Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5–11 years of age in Brazil: A prospective test-negative design study

ObjectiveTo estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5–11 years of age. MethodsThis prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5–11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. ResultsA total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). ConclusionIn this study with children 5–11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. Trial registration numberClinicalTrials.gov number, NCT05403307 (https://classic.clinicaltrials.gov/ct2/show/NCT05403307)

Comparison of Post-Vaccination Cellular Immune Response in Patients with Common Variable Immune Deficiency.

The problem of identifying vaccine-specific T-cell responses is still a matter of debate. Currently, there are no universal, clearly defined, agreed upon criteria for assessing the effectiveness of vaccinations and their immunogenicity for the cellular component of immunity, even for healthy people. But for patients with inborn errors of immunity (IEI), especially those with antibody deficiencies, evaluating cellular immunity holds significant importance. To examine the effect of one and two doses of inactivated adjuvanted subunit influenza vaccines on the expression of endosomal Toll-like receptors (TLRs) on the immune cells and the primary lymphocyte subpopulations in patients with common variable immunodeficiency (CVID). During 2018-2019, six CVID patients received one dose of a quadrivalent adjuvanted influenza vaccine; in 2019-2020, nine patients were vaccinated with two doses of a trivalent inactivated influenza vaccine. The proportion of key lymphocyte subpopulations and expression levels of TLRs were analyzed using flow cytometry with monoclonal antibodies. No statistically significant alterations in the absolute values of the main lymphocyte subpopulations were observed in CVID patients before or after vaccination with the different immunization protocols. However, after vaccination, a higher expression of TLR3 and TLR9 in granulocytes, monocytes, and lymphocytes was found in those patients who received two vaccine doses rather than one single dose. This study marks the first instance of using a simultaneous two-dose vaccination, which is associated with an elevated level of TLR expression in the immune cells. Administration of the adjuvanted vaccines in CVID patients appears promising. Further research into their impact on innate immunity and the development of more effective vaccination regimens is warranted.

Delivery and Safety of a Two-Dose Preventive Ebola Virus Disease Vaccine in Pregnant and Non-Pregnant Participants during an Outbreak in the Democratic Republic of the Congo.

During the 2018-2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group.

A cost benefit analysis of varicella vaccination in South Korea

BackgroundThe introduction of varicella vaccination has significantly reduced the burden of chickenpox in many countries, but outbreaks still occur in populations with high vaccination coverage. To address this, some countries, including the United States, Germany, and Japan, have adopted a two-dose varicella vaccination recommendation. Economic evaluations are crucial for assessing vaccine recommendations; however, there are limited studies exist in Asian countries. Thus, our study aimed to evaluate the cost-benefit of one-dose and two-dose varicella vaccination programs compared to no vaccination in South Korea, incorporating updated data on disease burden and costs. MethodsWe utilized data from South Korea’s health databases to estimate varicella burden and vaccination records. Decision tree analysis was employed to compare costs and benefits of vaccination strategies over a ten-year period for the 2012 birth cohort. Sensitivity analyses were conducted to assess the impact of various variables. ResultsBoth one-dose and two-dose vaccination programs showed cost-benefit compared to no vaccination, with substantial societal cost savings. The one-dose program yielded a benefit-cost ratio (BCR) of1.43, while the two-dose program had a direct BCR of1.28. Sensitivity analyses confirmed the robustness of these findings. ConclusionOur study demonstrates the economic benefits of varicella vaccination in South Korea, aligning with findings from other countries. While the second dose did not show additional cost savings compared to the one-dose program, other factors like disease severity and transmission dynamics should be considered. Implementing either a one-dose or two-dose varicella vaccination regimen in South Korea could lead to cost reductions and improved cost-effectiveness compared to no vaccination, emphasizing the importance of vaccination programs in reducing disease burden and enhancing public health outcomes.

The timing of local SARS-Cov-2 outbreaks and vaccination coverage during the Delta wave in Melbourne

ObjectiveThis article presents a longitudinal analysis of COVID-19 infection and vaccination coverage in Melbourne metropolitan local government areas (LGAs) during the 2021 Delta wave. MethodsCOVID-19 vaccination and infection data from 12 July to 27 November 2021 were sourced from government websites. Summary statistics and associated 95% confidence intervals (95% CI) were compared by LGA ranked according to socioeconomic status: total “burden” (total infections per thousand), “peak” (highest weekly infection rate), “lag” (interval between peak and 70% double vaccination). ResultsLGAs in the bottom five deciles for social advantage experienced higher infection rates (39.0 per thousand [95% CI: 38.5, 39.5] vs. 14.8 [14.7, 14.9]), and had lower two-dose vaccination coverage (23.8% [23.6, 23.9] vs. 32.7% [32.6, 32.7]) compared with LGAs in the top five deciles. LGAs that achieved 70% coverage two weeks or more after the infection peak experienced nearly twice the total infection burden (27.7 per 1000 [27.3, 28.0] compared with 14.9 [14.7, 15.0]) than LGAs with a shorter lag. ConclusionsExposure and transmission risk factors cluster within disadvantaged LGAs. The potential for large local outbreaks is heightened if vaccination uptake trails in these communities. Implications for Public HealthIn a pandemic, decision-makers must prioritise disease control and harm reduction interventions for at-risk LGAs.