Human Vaccines & Immunotherapeutics最新文献

Current influenza vaccines could be augmented by including recombinant neuraminidase (rNA) protein antigen to broaden protective immunity and improve efficacy. Toward this goal, we investigated formulation conditions to optimize rNA physicochemical stability. When rNA in sodium phosphate saline buffer (NaPBS) was frozen and thawed (F/T), the tetrameric structure transitioned from a "closed" to an "open" conformation, negatively impacting functional activity. Hydrogen deuterium exchange experiments identified differences in anchorage binding sites at the base of the open tetramer, offering a structural mechanistic explanation for the change in conformation and decreased functional activity. Change to the open configuration was triggered by the combined stresses of acidic pH and F/T. The desired closed conformation was preserved in a potassium phosphate buffer (KP), minimizing pH drop upon freezing and including 10% sucrose to control F/T stress. Stability was further evaluated in thermal stress studies where changes in conformation were readily detected by ELISA and size exclusion chromatography (SEC). Both tests were suitable indicators of stability and antigenicity and considered potential critical quality attributes (pCQAs). To understand longer-term stability, the pCQA profiles from thermally stressed rNA at 6 months were modeled to predict stability of at least 24-months at 5°C storage. In summary, a desired rNA closed tetramer was maintained by formulation selection and monitoring of pCQAs to produce a stable rNA vaccine candidate. The study highlights the importance of understanding and controlling vaccine protein structural and functional integrity.

Despite the ongoing global vaccination campaign aimed at preventing human papillomavirus (HPV) related health issues, the uptake of the HPV vaccine remains unacceptably low in developing regions, particularly in sub-Saharan Africa (SSA). Therefore, this systematic review and meta-analysis aimed at determining the pooled prevalence and associated factors of HPV vaccine uptake among adolescent school girls in SSA. Electronic bio-medical databases were explored. Pooled prevalence, publication bias, meta-regression, sub-group, and sensitivity analysis were performed. The estimated pooled prevalence of HPV vaccine uptake was 28.53% [95% CI: (5.25, 51.81)]. Having good knowledge and a positive attitude was significantly associated with HPV vaccine uptake in SSA. Subgroup analysis revealed the highest uptake was 62.52% from Kenya and the lowest was 3.77% in Nigeria. The HPV vaccine uptake is low. It underscores the need for community education, school-based immunization, and education programs that promote the uptake of the vaccine to increase coverage.

Coronavirus disease 2019 (COVID-19) was extraordinarily harmful, with high rates of infection and hospitalization. This study aimed to evaluate the impact of COVID-19 vaccination status and other factors on hospitalization and disease severity, using data from Nagasaki Prefecture, Japan. Confirmed cases of COVID-19 infection with vaccination status were included and the differences in characteristics between different vaccination statuses, hospitalization or not, and patients with varying levels of disease severity were analyzed. Furthermore, logistic regression was used to calculate odds ratio (ORs) and 95% confidence intervals (CI) to evaluate the association of various factors with hospitalization and disease severity. From March 14, 2020 to August 31, 2022, 23,139 patients were unvaccinated 13,668 vaccinated the primary program with one or two doses, and 4,575 completed the booster. Vaccination reduced the risk of hospitalization with an odd ratio of 0.759 (95% CI: 0.654-0.881) and the protective effect of completed booster vaccination was more pronounced (OR: 0.261, 95% CI: 0.207-0.328). Similarly, vaccination significantly reduced the risk of disease severity (vaccinated primary program: OR: 0.191, 95% CI: 0.160-0.228; completed booster vaccination: OR: 0.129, 95% CI: 0.099-0.169). Overall, unvaccinated, male, elderly, immunocompromised, obese, and patients with other severe illness factors were all risk factors for COVID-19-related hospitalization and disease severity. Vaccination was associated with a decreased risk of hospitalization and disease severity, and highlighted the benefits of completing booster.

Despite the availability of school-based immunization programs (SBIPs) in Canada, human papillomavirus (HPV) vaccine uptake remains suboptimal. Vaccine education may improve vaccine uptake among adolescents. The objective of this qualitative study was to identify opportunities for HPV vaccine education in British Columbia, Canada, by exploring the perspectives of students, parents, school staff, and public health nurses on the current SBIP. Individual semi-structured interviews were conducted with adult participants and focus groups were conducted with grade 6 students between November 2019 and May 2020. The interviews and focus groups were transcribed and then analyzed using reflexive thematic analysis. Opportunities for HPV vaccine education were identified in three themes: 1) making SBIPs student-centered; 2) adopting a collaborative and interdisciplinary approach to vaccine education; and 3) actualizing parent education opportunities. Broad support existed for a formal, collaborative HPV grade 6 vaccine curriculum delivered by teachers and public health nurses to provide evidence-based health information. Participants voiced that the curriculum should integrate students' perspectives on topics of interest and address needle associated pain and anxiety. Parents were identified as the primary vaccine decisionmakers, therefore, participants stated it was crucial to also provide parent-directed vaccine education as part of SBIP. Our findings support the development of a collaborative HPV vaccine curriculum directed to and informed by students and parents to buttress current SBIPs in British Columbia.

Individuals who have Long COVID may have unique perspectives about COVID-19 vaccination due to the significant impact that COVID-19 has had on their lives. However, little is known about the specific vaccination perspectives among this patient population. The goal of our study was to improve our understanding of perspectives about COVID-19 vaccines among individuals with Long COVID. Interviews were conducted with patients receiving care at a post-COVID recovery clinic. Deductive thematic analysis was used to characterize participant perspectives according to the vaccine acceptance continuum framework, which recognizes a spectrum from vaccine acceptance to refusal. From interviews with 21 patients, we identified perspectives across the continuum of vaccine acceptance. These perspectives included acceptance of vaccines to prevent future illness, concerns about vaccine side effects on Long COVID symptoms, and refusal of vaccines due to perceived natural immunity. A limitation of our study is that these perspectives are specific to individuals receiving care at one post-COVID recovery clinic. In conclusion, our study demonstrates that some patients with Long COVID are uncertain about COVID-19 vaccines and boosters but may also be amenable to conversations that impact future vaccination acceptance. Patient perspectives should be considered when communicating recommendations for COVID-19 vaccinations to this population.

Global COVID-19 vaccination programs effectively contained the fast spread of SARS-CoV-2. Characterizing the immunity status of returned populations will favor understanding the achievement of herd immunity and long-term management of COVID-19 in China. Individuals were recruited from 7 quarantine stations in Guangzhou, China. Blood and throat swab specimens were collected from participants, and their immunity status was determined through competitive ELISA, microneutralization assay and enzyme-linked FluoroSpot assay. A total of 272 subjects were involved in the questionnaire survey, of whom 235 (86.4%) were returning Chinese individuals and 37 (13.6%) were foreigners. Blood and throat swab specimens were collected from 108 returning Chinese individuals. Neutralizing antibodies against SARS-CoV-2 were detected in ~90% of returning Chinese individuals, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compared with the prototype virus. However, memory T-cell responses, including specific IFN-γ and IL-2 responses, were not different in either group. Smoking, alcohol consumption, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concern. The vaccine dose was the unique common influencing factor for Omicron subvariants. Enhanced immunity against SARS-CoV-2 was established in returning Chinese individuals who were exposed to reinfection and vaccination. Domestic residents will benefit from booster homologous or heterologous COVID-19 vaccination after reopening of China, which is also useful against breakthrough infection.

The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies (nAbs) were analyzed at 2 and 12 weeks after immunization. Participants in the low and high CD4+ groups had mean CD4+ counts of 139 and 575 cell/µL, respectively. Two and 12 weeks after immunization, in the low CD4 group, the median anti-RBD-IgG levels were 159 IU/mL and 143 IU/mL, respectively, whereas the nAb level was 71% and decreased to 47.2%, respectively. Contrarily, the median anti-RBD-IgG levels in the high CD4+ group were 273 IU/mL and 294 IU/mL, respectively, whereas the nAb levels were 89.3% and relatively stable at 81.6%. However, although immune responses between the two study groups were not significantly different, a decline in nAb levels was observed at 12 weeks in the low CD4+ group. Therefore, a COVID-19 booster vaccine dose is suggested for immunoprotection.

The mechanisms of Pythium insidiosum-antigen (PIA) immunotherapy activating a patient's immune system are unknown. We evaluated the interleukin-8 (IL-8) serum levels during P. insidiosum infection and after vaccination with PIA in vascular pythiosis cases. Furthermore, we studied the anti-P. insidiosum activity of neutrophils stimulated with various concentrations of PIA ex vivo in 3 strains of P. insidiosum isolated from vascular pythiosis patients. IL-8 serum levels were evaluated using the ELISA technique. We assessed the effect of PIA-stimulated neutrophils on the viability of zoospores using MTT assay, visualized neutrophil extracellular trap (NET) formation via microscopy, and measured the levels of double-stranded DNA (dsDNA) using PicoGreen dsDNA quantitation assay in 3 strains of P. insidiosum isolated from vascular pythiosis patients. Serum levels of IL-8 gradually lowered from the early to the end phases of vaccination with PIA among the surviving group of vascular pythiosis cases. Neutrophils stimulated with 0.01 µg/ml PIA reduced zoospore viability significantly compared to PIA-unstimulated neutrophils for strain 1 and strain 3 (p < .05). Neutrophils stimulated with 0.01, 0.1, 1, and 10 µg/ml PIA exhibited significantly lower zoospore viability than PIA-unstimulated neutrophils for strain 2 (p < .05). IL-8 can be used as a biomarker for monitoring vascular pythiosis cases treated with the PIA vaccine. Also, anti-P. insidiosum activity of PIA-stimulated neutrophils was probably due to the disruption of cellular activity in zoospores rather than the mechanisms based on the formation of NETs.

Meningococcal vaccination strategies in China are intricate, including multiple vaccines targeting different serogroups. The current National Immunization Program (NIP) includes two polysaccharide vaccines for serogroups A and C (MPV-A and MPV-AC), covering limited serogroups and requiring adaptation. This study aims to evaluate the cost-effectiveness of replacing the current strategy with alternative strategies utilizing non-NIP vaccines to inform policy decisions. From a societal perspective, a decision tree-Markov model was constructed to simulate the economic and health consequences of meningococcal disease in a 2019 birth cohort with four vaccination strategies. Epidemiology, vaccine efficacy, cost, and other parameters were derived from previous studies. We conducted sensitivity analyses to assess the robustness of the findings and explored prices for non-NIP vaccines that enable cost-effective strategies. Compared to the current strategy, alternative strategies using quadrivalent polysaccharide vaccine (MPV-4), bivalent conjugate vaccine (MCV-AC), and quadrivalent conjugate vaccine (MCV-4) could avoid 91, 286, and 455 more meningococcal cases. The ICERs were estimated at approximately $250 thousand/QALY, $450 thousand/QALY, and $1.5 million/QALY, all exceeding the threshold of three times GDP per capita. The alternative strategies were not cost-effective. However, if vaccine prices were reduced to $3.9 for MPV-4, $9.9 for MCV-AC, and $12 for MCV-4, the corresponding strategy would be cost-effective. The current meningococcal vaccination strategy in China could effectively prevent the disease at a low cost, but with limited serogroup coverage. Strategies using MPV-4, MCV-AC, or MCV-4 could increase health benefits at a substantial cost, and might become cost-effective if vaccine prices decrease.

This is a response to Marchand & Masoud's response letter regarding my criticism "Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies."" The response is a defense of the initial criticism to the paper regarding the validity of the inclusion of Ladapo´s paper.