Xuanxuan Nian

Influenza vaccine effectiveness exhibits significant heterogeneity across age groups, largely shaped by lifelong immune remodeling. This review adopts a continuous spectrum perspective-spanning immune development, immune maturation, and immunosenescence-to delineate host immune responses to influenza across different life stages. Subsequently, the influence of these age-dependent differences on vaccine effectiveness is discussed. Based on these insights, an age-specific vaccine development strategy is proposed to guide differentiated vaccine optimization approaches for children, adults, and the elderly. This review provides a theoretical basis for transitioning from a “one-dose-fits-all” vaccination model and toward an age-specific precision paradigm.

Objectives: Seasonal influenza leads to substantial global morbidity and mortality, especially in adults aged 65 years and older, who present poor immune responses to standard-dose influenza vaccines. This study aimed to systematically evaluate the preclinical safety and immunogenicity of a high-dose quadrivalent seasonal influenza split vaccine (HD-QIV), providing preclinical evidence for its clinical application in the elderly. Methods: Following GLP guidelines, we performed single-dose and repeated-dose toxicity tests in Sprague–Dawley rats, active systemic anaphylaxis assays in guinea pigs, and immunogenicity assessments in young and aged BALB/c mice. Safety indicators included general clinical signs, hematology, blood biochemistry, histopathology and allergic reactions; immunogenicity was evaluated via hemagglutination inhibition (HI) antibody titers and antigen-specific cellular immune responses. Results: HD-QIV only caused mild and reversible local irritation in rats without obvious systemic toxicity, and no dose-related systemic anaphylaxis was observed in guinea pigs. HD-QIV induced robust and dose-dependent humoral immune responses, and showed significantly higher HI antibody titers, earlier seroconversion and longer antibody persistence than standard quadrivalent influenza vaccine in aged mice. Cellular immunity was slightly enhanced but not the dominant protective response. Conclusions: The HD-QIV demonstrates favorable preclinical safety and superior immunogenicity, supporting its further clinical development and use as a priority vaccine for the elderly population.

Madin–Darby canine kidney (MDCK) cells are commonly used to produce cell-based influenza vaccines. However, the role of the low-serum medium on the proliferation of MDCK cells and the propagation of the influenza virus has not been well studied. In the present study, we used 5 of 15 culture methods with different concentrations of a mixed medium and neonatal bovine serum (NBS) to determine the best culture medium. We found that a VP:M199 ratio of 1:2 (3% NBS) was suitable for culturing MDCK cells. Furthermore, the stable growth of MDCK cells and the production of the influenza virus were evaluated over long-term passaging. We found no significant difference in terms of cell growth and virus production between high and low passages of MDCK cells under low-serum culture conditions, regardless of influenza virus infection. Lastly, we performed a comparison of the transcriptomics and proteomics of MDCK cells cultured in VP:M199 = 1:2 (3% NBS) with those cultured in VP:M199 = 1:2 (5% NBS) before and after influenza virus infection. The transcriptome analysis showed that differentially expressed genes were predominantly enriched in the metabolic pathway and MAPK signaling pathway, indicating an activated state. This suggests that decreasing the concentration of serum in the medium from 5% to 3% may increase the metabolic activity of cells. Proteomics analysis showed that only a small number of differentially expressed proteins could not be enriched for analysis, indicating minimal difference in the protein levels of MDCK cells when the serum concentration in the medium was decreased from 5% to 3%. Altogether, our findings suggest that the screening and application of a low-serum medium provide a background for the development and optimization of cell-based influenza vaccines.

The authors would like to make the following corrections to this published paper

H5N1 highly pathogenic avian influenza virus (HPAIV) infections pose a significant threat to human health, with a mortality rate of around 50%. Limited global approval of H5N1 HPAIV vaccines, excluding China, prompted the need to address safety concerns related to MDCK cell tumorigenicity. Our objective was to improve vaccine safety by minimizing residual DNA and host cell protein (HCP). We developed a downstream processing method for the cell-based H5N1 HPAIV vaccine, employing Capto^TM Core 700, a multimodal resin, for polishing. Hydrophobic-interaction chromatography (HIC) with polypropylene glycol as a functional group facilitated the reversible binding of virus particles for capture. Following the two-step chromatographic process, virus recovery reached 68.16%. Additionally, HCP and DNA levels were reduced to 2112.60 ng/mL and 6.4 ng/mL, respectively. Western blot, high–performance liquid chromatography (HPLC), and transmission electron microscopy (TEM) confirmed the presence of the required antigen with a spherical shape and appropriate particle size. Overall, our presented two-step downstream process demonstrates potential as an efficient and cost-effective platform technology for cell-based influenza (H5N1 HPAIV) vaccines.

The resurgence of pertussis in vaccinated communities may be related to the reduced long-term immunity induced by acellular pertussis vaccines. Therefore, developing improved pertussis vaccine candidates that could induce strong Th1 or Th17 cellular immunity is an urgent need. The use of new adjuvants may well meet this requirement. In this research, we developed a novel adjuvant candidate by combining liposome and QS-21 adjuvant. Adjuvant activity, protective efficacy, the level of neutralizing antibody against PT, and the resident memory T (T_RM) cells in lung tissue after vaccination were studied. We then performed B. pertussis respiratory challenge in mice after they received vaccination with traditional aluminum hydroxide and the novel adjuvant combination. Results showed that the liposome + QS-21 adjuvant group had a rapid antibody and higher antibody (PT, FHA, Fim) level, induced anti-PT neutralizing antibody and recruited more IL-17A-secreting CD4⁺ T_RM cells along with IL-17A-secreting CD8⁺ T_RM cells in mice, which provided robust protection against B. pertussis infection. These results provide a key basis for liposome + QS-21 adjuvant as a promising adjuvant candidate for developing an acellular pertussis vaccine that elicits protective immunity against pertussis.

Pertussis (whooping cough) is a respiratory disease caused primarily by Bordetella pertussis, a Gram-negative bacteria. Pertussis is a relatively contagious infectious disease in people of all ages, mainly affecting newborns and infants under 2 months of age. Pertussis is undergoing a resurgence despite decades of high rates of vaccination. To better cope with the challenge of pertussis resurgence, we evaluated its possible causes and potential countermeasures in the narrative review. Expanded vaccination coverage, optimized vaccination strategies, and the development of a new pertussis vaccine may contribute to the control of pertussis.

Gene therapy is a technique involving the modification of an individual’s genes for treating a particular disease. The key to effective gene therapy is an efficient carrier delivery system. Viral vectors that have been artificially modified to lose their pathogenicity are used widely as a delivery system, with the key advantages of their natural high transduction efficiency and stable expression. With decades of development, viral vector-based gene therapies have achieved promising clinical outcomes. Currently, the three key vector strategies are based on adeno-associated viruses, adenoviruses, and lentiviruses. However, certain challenges, such as immunotoxicity and “off-target”, continue to exist. In the present review, the above three viral vectors are discussed along with their respective therapeutic applications. In addition, the major translational challenges encountered in viral vector-based gene therapies are summarized, and the possible strategies to address these challenges are also discussed.

Influenza prevention and control has been one of the biggest challenges encountered in the public health domain. The vaccination against influenza plays a pivotal role in the prevention of influenza, particularly for the elderly and small children. According to the epidemiology of influenza in China, the nation is under a heavy burden of this disease. Therefore, as a contribution to the prevention and control of influenza in China through the provision of relevant information, the present report discusses the production and batch issuance of the influenza vaccine, analysis of the vaccination status and vaccination rate of the influenza vaccine, and the development trend of the influenza vaccine in China.

Viruses, bacteria, fungi, and several other pathogenic microorganisms usually infect the host via the surface cells of respiratory mucosa. Nasal vaccination could provide a strong mucosal and systemic immunity to combat these infections. The intranasal route of vaccination offers the advantage of easy accessibility over the injection administration. Therefore, nasal immunization is considered a promising strategy for disease prevention, particularly in the case of infectious diseases of the respiratory system. The development of a nasal vaccine, particularly the strategies of adjuvant and antigens design and optimization, enabling rapid induction of protective mucosal and systemic responses against the disease. In recent times, the development of efficacious nasal vaccines with an adequate safety profile has progressed rapidly, with effective handling and overcoming of the challenges encountered during the process. In this context, the present report summarizes the most recent findings regarding the strategies used for developing nasal vaccines as an efficient alternative to conventional vaccines.