Notes

Modern Proper care in Heart Failure: Demanding Prognostication.
to recruit patients based on the disease burden, which enables measurements of treatment outcomes by race and promotes health equity.Thailand has implemented single-dose mumps-containing vaccines since 1997 and two doses since 2010. This study aimed to describe the seroprevalence of mumps among children who received one- or two-dose mumps vaccines. A cross-sectional study of 145 children (aged 3-9 years) and 422 adolescents (10-18 years) was conducted. Mumps IgG seropositivity was defined as ≥ 22 RU/mL by EUROIMMUN ELISA method. The mumps seroprevalence was higher in children (82.1%, 95% CI 74.8-87.9) compared to adolescents (41.7%, 95% CI 37.0-46.6) who had received at least one dose of the mumps vaccine. Among those receiving 2 doses of mumps vaccine at ≥ 5 years after their last mumps vaccination, only 51.3% had maintained IgG ≥ 22 RU/ml. There was a reverse correlation between mumps IgG titer and the time interval from the second dose of mumps vaccine (R = -0.44, p less then 0.001). A booster dose of MMR vaccine in young adults may be needed.
As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country.

Peripheral blood mononuclear cells were collected from a subset of 67 participants≥10years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-γ, TNF-α and IL-2 responses were assessed by flow cytometry.

Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-γ+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-γ+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-γ+TNF-α+IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells.

TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
Previous studies evaluated the SARS-CoV-2 vaccine safety or compared adverse events following vaccination to those from infection. Limited data about the impact of prior infection on post-vaccine adverse events are available. The objective of this study was to evaluate the impact of prior SARS-CoV-2 infection on outcomes shortly after vaccination using a longitudinal design.

Nationwide, multicenter, retrospective cohort study of hospitalization, death, and pre-specified adverse event rates among Veterans who received mRNA vaccines within the Veterans Health Administration between 12/11/2020 and 8/31/2021. Daily incidence rates were compared before and after vaccine doses, stratified by history of microbiologically-confirmed SARS-CoV-2.

3,118,802 patients received a first dose and 2,979,326 a second, including 102,829 with a history of SARS-CoV-2 infection. Daily incident hospitalization rates were unchanged before and after the second dose among patients without previous infection (28.8/100,000 post-dose versus 28.6/100,000 pre-dose, p=0.92). In previously-infected patients, the hospitalization rate increased above baseline one day following vaccination (158.2/100,000 after dose 2 versus 57.3/100,000 pre-dose, p<0.001), then returned to baseline. Chart review indicated vaccine side effects, such as fever, constitutional symptoms, weakness, or falls, as the definite (39%) or possible (18%) cause of hospitalization. Affected patients had mean age 75, and 90% had at least one serious comorbidity. Hospitalizations were brief (median 2days), with rapid return to baseline health. Worse baseline health among previously-infected patients prevented conclusions about mortality risk.

Two-dose mRNA vaccine regimens are safe in a population with many comorbidities. Transient increased risks of hospitalization were identified among patients with prior SARS-CoV-2, absolute risk ∼11000. Findings support additional study regarding the optimal dosing schedule in this population.

None.
None.
Over the last 2 decades, Haemophilus influenzae type a (Hia) has emerged as a significant cause of invasive disease in some geographic regions and populations. Recognition of the importance of Hia in the etiology of serious disease, particularly in young children, prompted the development of a new protein-capsular polysaccharide conjugate vaccine, similar in design to a vaccine against H. influenzae type b. At present, understanding of Hia immunology is incomplete; the immunological correlate of protection against invasive disease is unknown.

Our objective was to study Hia antibody in children of various ages residing in a Canadian province with low incidence rates of invasive disease. The enzyme-linked immunosorbent assays were performed to quantify plasma IgG and IgM specific to Hia capsular polysaccharide in 133 children (3months to 16years).

Both anti-Hia IgG and IgM concentrations increased with age and were significantly higher in older children; a positive correlation between age and concentratiody. However, the carriage rates of Hia in the region are unknown and further seroepidemiological studies are warranted. Although natural antibody may protect certain population groups against invasive disease, immunization of younger children will be essential to prevent serious infections if Hia continues to spread across North America.Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis, proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. https://www.selleckchem.com/products/mycro-3.html When the T cellular response was evaluated, two peptides P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN-) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis.The rapid spread of the COVID-19 pandemic, with its devastating medical and economic impacts, triggered an unprecedented race toward development of effective vaccines. The commercialized vaccines are parenterally administered, which poses logistic challenges, while adequate protection at the mucosal sites of virus entry is questionable. Furthermore, essentially all vaccine candidates target the viral spike (S) protein, a surface protein that undergoes significant antigenic drift. This work aimed to develop an oral multi-antigen SARS-CoV-2 vaccine comprised of the receptor binding domain (RBD) of the viral S protein, two domains of the viral nucleocapsid protein (N), and heat-labile enterotoxin B (LTB), a potent mucosal adjuvant. The humoral, mucosal and cell-mediated immune responses of both a three-dose vaccination schedule and a heterologous subcutaneous prime and oral booster regimen were assessed in mice and rats, respectively. Mice receiving the oral vaccine compared to control mice showed significantly enhanced post-dose-3 virus-neutralizing antibody, anti-S IgG and IgA production and N-protein-stimulated IFN-γ and IL-2 secretion by T cells. When administered as a booster to rats following parenteral priming with the viral S1 protein, the oral vaccine elicited markedly higher neutralizing antibody titres than did oral placebo booster. A single oral booster following two subcutaneous priming doses elicited serum IgG and mucosal IgA levels similar to those raised by three subcutaneous doses. In conclusion, the oral LTB-adjuvanted multi-epitope SARS-CoV-2 vaccine triggered versatile humoral, cellular and mucosal immune responses, which are likely to provide protection, while also minimizing technical hurdles presently limiting global vaccination, whether by priming or booster programs.Since the beginning of the COVID-19 pandemic, the development of effective vaccines against this pathogen has been a priority for the scientific community. Several strategies have been developed including vaccines based on recombinant viral protein fragments. The receptor-binding domain (RBD) in the S1 subunit of S protein has been considered one of the main targets of neutralizing antibodies. In this study we assess the potential of a vaccine formulation based on the recombinant RBD domain of SARS-CoV-2 expressed in the thermophilic filamentous fungal strain Thermothelomyces heterothallica and the hepatitis B virus (HBV) core protein. Functional humoral and cellular immune responses were detected in mice. To our knowledge, this is the first report on the immune evaluation of a biomedical product obtained in the fungal strain T. heterothallica. These results together with the intrinsic advantages of this expression platform support its use for the development of biotechnology products for medical purpose.
Although nearly all Australian children are vaccinated against pneumococcal disease, pneumococcal vaccine uptake is low among high-risk adults. This study aimed to identify perceived barriers to pneumococcal vaccination among high-risk adults.

This paper reports combined data on pneumococcal vaccination collected from three different online, cross-sectional surveys that were administered in Australia between August 2019 and September 2020. Using Poisson regression, we identified characteristics and beliefs associated with self-reported pneumococcal vaccination among adults aged 65 and over or with chronic health conditions.

The weighted estimate for pneumococcal vaccine coverage was 24% for high-risk adults under 65 and 53% for adults aged 65 and over. Nearly half of those under 65 reported they had never heard of the pneumococcal vaccine, while 26% of those aged 65 and over had never heard of the vaccine. Among those under 65, pneumococcal vaccination was associated with high perceived disease susceptibility (PR=1.
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