Human Vaccines & Immunotherapeutics最新文献

The World Health Organization (WHO) has shifted from a multiple-dose human papillomavirus (HPV) vaccine schedule to a one-dose schedule prioritizing females aged 9-14 y. Given the burden of HPV-associated disease aside from cervical cancer and affecting both sexes, a shift toward emphasizing gender-neutral HPV vaccination strategies may improve vaccination coverage and more comprehensively address HPV-driven disease across both sexes, particularly for low- and middle-income countries.

Influenza B/Victoria viruses predominated during the 2021-2022 influenza season in Beijing, China, unlike most northern hemisphere countries, likely due to reduced international travel. We estimated influenza vaccine effectiveness (VE) against the B/Victoria lineage to provide a more comprehensive evaluation of 2021-2022 influenza VE. Between October 2021 and April 2022, patients aged ≥6 months with influenza-like illness (ILI) visiting outpatient departments in Beijing's influenza virological surveillance system were enrolled. A test-negative design was used to assess VE against influenza B/Victoria, adjusting for sex, age groups, the presence of chronic diseases, onset-to-enrollment interval, and symptom onset timing. Of the 8,813 eligible patients, 1,787 (20.3%) tested positive for influenza B/Victoria only. 573/8813 (6.5%) were vaccinated against influenza. The adjusted effectiveness against B/Victoria for all ages was 16.6% (95% CI: -7.5% to 35.2%) overall. VE was low against influenza B/Victoria among medically attended ILI patients during the 2021-2022 season in Beijing, China.

This bibliometric and visualization study provides a comprehensive analysis of global research hotspots and trends in DNA vaccine research from 2014 to 2024. By employing data sourced from the Web of Science Core Collection, we identified a total of 3,600 articles. Our analysis reveals a declining trend in annual publications. Active countries, institutions, journals, and authors were identified, with China, the Pasteur Network, the Vaccine Journal, and David B Weiner being the most prolific contributors. Keywords cluster analysis distinguished four major research directions: infectious disease and immunity, viral challenge and vaccine development, optimization of DNA vaccine delivery systems, and cancer and immunotherapy research. The literature co-citation analysis revealed four major research hotspots, including DNA vaccines for Zika virus, human papillomavirus (HPV), and COVID-19, as well as safety, efficacy, and immunogenicity studies of DNA vaccines. Concurrently, the burst citation analysis identified emerging themes, including the development of DNA vaccines for COVID-19, Ebola, and MERS-CoV, as well as innovations in antigen design and delivery technologies. This study offers valuable insights into the evolution and future directions of DNA vaccine research, emphasizing its importance for global public health and the potential to address current and future health challenges.

Antagonism of the neonatal Fc receptor through an engineered antibody Fc fragment, such as efgartigimod, results in a decrease in immunoglobulin G levels. This approach is being evaluated as a therapeutic strategy for the treatment of IgG-mediated autoimmune diseases. Our goal was to evaluate the impact of mFc-ABDEG, a mouse-adapted antibody Fc fragment with a mode of action highly similar to efgartigimod, on vaccine-induced protective immune responses against viral infections. Therefore, mouse vaccination models for COVID-19 and influenza were employed, utilizing an mRNA COVID-19 vaccine (COMIRNATY) and an adjuvanted, inactivated quadrivalent influenza vaccine (Seqirus+AddaVax), respectively. In both models, vaccination induced robust humoral responses. As expected, animals treated with mFc-ABDEG had lower levels of virus-specific IgG, while virus-specific IgM responses remained unaffected. The COVID-19 vaccine induced a strong Th1-type T cell response irrespective of mFc-ABDEG treatment. Influenza vaccination resulted in a poor T cell induction, regardless of mFc-ABDEG treatment, due to the Th2-biased response that inactivated influenza vaccines typically induce. Importantly, mFc-ABDEG treatment had no effect on protective immunity against live viral challenges in both models. Vaccinated animals treated with mFc-ABDEG were equally protected as the non-treated vaccinated controls. These non-clinical data demonstrate that FcRn antagonism with mFc-ABDEG did not affect the generation of vaccine-induced protective humoral and cellular responses, or protection against viral challenges. These data substantiate the clinical observations that, although IgG titers were reduced, FcRn antagonism with efgartigimod did not impair the ability to generate new specific IgG responses, regardless of the timing of vaccination.

Considering the increasing use of immune checkpoint inhibitors in cancer treatment, our aim is to report a rare cutaneous immune-related adverse event induced by PD-1 inhibitor pembrolizumab and provide a brief overview of pembrolizumab-induced subacute cutaneous lupus erythematosus (SCLE) cases in the literature. We report a 67-year-old woman with oropharyngeal squamous cell carcinoma who developed SCLE during treatment with pembrolizumab. After 18 weeks (sixth cycle) of pembrolizumab immunotherapy, a widespread pruritic erythematous rash evaluated as grade 3 immune-related adverse event appeared primarily on the patient's limbs. Histopathological examination and direct immunofluorescence showed characteristic features of SCLE. The patient was treated with oral prednisone 40 mg daily and topical corticosteroids. In 2 weeks, her rash had cleared up significantly and her pruritus had disappeared. SCLE is an infrequent but recognized immune-related adverse event linked to pembrolizumab treatment.

Although neo-antigen mRNA vaccines are promising for personalized cancer therapy, their effectiveness is often limited by the immunosuppressive tumor microenvironment (TME). The adenosine A₂A receptor (A₂AR) inhibits dendritic cell (DC) function and weakens antitumor T cell responses through hypoxia-driven mechanisms within the TME. This review explores a novel strategy combining neo-antigen mRNA vaccines with A₂AR antagonists (A₂ARi). By targeting A₂AR, this approach reduces TME-induced immunosuppression, enhances DC activation, and improves neo-antigen presentation. The review also discusses lipid nanoparticles (LNPs) to co-deliver A₂ARi and mRNA vaccines, optimizing their effectiveness. The integration of neo-antigen mRNA-LNPs with A₂ARi modulation offers a promising strategy to overcome immunosuppression, stimulate DC activation, and achieve precise anti-tumor responses with minimal off-target effects. This synergy represents significant progress in cancer immunotherapy, advancing the potential for personalized neoantigen therapies.

The coronavirus disease (COVID-19) pandemic accelerated development of various vaccine platforms. Among them, mRNA vaccines played a crucial role in controlling the pandemic due to their swift development and efficacy against virus variants. Despite the success of these vaccines, recent studies highlight challenges in evaluating vaccine efficacy, especially in individuals with prior COVID-19 infection. Weakened neutralizing antibody responses after additional doses are observed in these populations, raising concerns about using neutralizing antibody titers as the sole immune correlate of protection. While neutralizing antibodies remain the primary endpoint in immunogenicity trials, they may not fully capture the immune response in populations with widespread prior infection or vaccination. This review explores reduced neutralizing antibody responses in previously infected individuals, and their impact on vaccine efficacy evaluation. It also offers recommendations for improving efficacy assessment, stressing incorporation of additional immune markers such as cell-mediated immunity to enable more comprehensive understanding of vaccine-induced immunity.

Respiratory syncytial virus (RSV) is a highly contagious pathogen and a leading cause of severe lower respiratory tract illness (LRTI) in infants and young children, irrespective of risk factors. Nirsevimab, an extended half-life monoclonal antibody, was approved in Canada in 2023 as a passive immunizing agent for the prevention of RSV LRTI. This study evaluated the optimal price per dose (PPD) at commonly accepted willingness-to-pay (WTP) thresholds among Canadian infants compared to the current standard of care (i.e. palivizumab for preterm infants and those with specific medical conditions). A static decision tree model was developed to assess the impact of nirsevimab on RSV-related health and economic outcomes among Canadian infants - including outpatient physician and emergency department visits, inpatient hospitalizations including intensive care unit (ICU) admissions and mechanical ventilation, and the associated healthcare costs of these outcomes. The model utilized Canadian epidemiological and cost inputs where possible, adopting a societal perspective. Compared to the standard of care, nirsevimab was expected to prevent 47,609 RSV-related health events, including 2,296 hospitalizations and a reduction of approximately $45 million in direct healthcare costs. At a WTP threshold of $50,000 per quality-adjusted life-year (QALY), the estimated base case PPD was $536, based on average cost assumptions across several costing scenarios. These findings suggest that universal immunization with nirsevimab could significantly reduce the health and economic burden of RSV among Canadian Infants.

Globally, there are over 3 million severe cases of influenza each year, leading to up to half a million deaths. This study provides a comprehensive analysis of the current status of children's influenza vaccine research over the past 20 years and explores potential future research trends, including improvements in vaccine coverage and strategies to address vaccine hesitancy. We extracted all research data on children's influenza vaccines from 2004 to 2024 using the Web of Science Core Collection (WOSCC). The contributions of various countries/regions, institutions, authors, and journals in this field were assessed, and research hotspots as well as promising future trends were predicted through keyword analysis using CiteSpace and VOSviewer. A total of 2,598 related publications from 2004 to 2024 were identified and collected for analysis. The United States (USA) and England emerged as the leading contributors with the highest number of published papers. AstraZeneca was identified as a key leader among research institutions, and Ambrose Christopher S was recognized as the most productive author in this field. The journals Vaccine and Human Vaccines & Immunotherapeutics stood out as the most prominent publications in this area. The keyword analysis highlighted that international research collaboration maybe a promising strategy for bridging global gaps; Addressing vaccine hesitancy could potentially increase vaccination coverage; Live attenuated vaccines, intranasal administration and universal vaccines are promising directions for future development. These insights highlight potential avenues for improving influenza vaccine coverage and inform strategies to mitigate vaccine hesitancy, crucial for protecting children and enhancing public health.