Human Vaccines & Immunotherapeutics最新文献

This study reports on the long-term stability of a recombinant 9-valent HPV vaccine, addressing a gap in the literature as previous research did not extend beyond 72 months. The vaccine targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and was produced using an E. coli expression system. We optimized soluble HPV L1 protein expression by truncating the N- and C-termini, resulting in HPV L1 virus-like particles (VLPs). Structural analysis confirmed the VLPs' resemblance to natural ones, suitable for vaccine production. Stability testing encompassed appearance, dosage, pH, osmolarity, aluminum content, polysorbate 80, in vitro relative potency, abnormal toxicity, in vivo potency, sterility, and endotoxin levels. The vaccine showed stability under extreme conditions of light (4500 lx) and shaking table vibration (10-30 rpm) for at least 7 days at 5 ± 3°C. Long-term storage at 5 ± 3°C maintained stability for up to 72 months, while accelerated testing at 25 ± 2°C showed stability for at least 12 months. The findings suggest that the vaccine's potency is best preserved under protection from high temperatures and direct light, with even harsh conditions not significantly compromising stability. This enhances the global distribution potential of the HPV vaccine.

WHO had warned of the impending "X disease," emphasizing the need to quickly establish an immune barrier. The willingness of vaccination staff to recommend vaccines was crucial in such scenarios. This study aimed to investigate willingness and influencing factors of Non-EPI Vaccines recommendations among Chinese vaccination staff in Hangzhou, China. We selected vaccination staff in 191 vaccination clinics from Hangzhou for a questionnaire-based survey using a cross-sectional survey. Descriptive statistics were made on the characteristics of participants. Univariate and multivariable analyses were used to determine the influencing factors of Non-EPI Vaccines recommendations. The overall recommendation rate was 76.2%. Compared to Supplementary and Individual Non-EPI Vaccines, vaccination staff were more willing to recommend Alternative ($x^2$ = 215.655, P < 0.05) and Combined Non-EPI Vaccines ($x^2$ = 214.998, P < 0.05). Multivariate logistic regression analysis showed that vaccination staff who did not participate in COVID-19 vaccination work (OR = 2.942, 95%CI:1.121 ~ 9.302), believe they had an obligation to recommend Non-EPI Vaccines (OR _disagree = 7.957, 95%CI:1.238 ~ 87.69; OR _neutrality = 4.187, 95%CI:1.66 ~ 10.563), and think that the effects of non-routine immunization vaccines were very good (OR _disagree = 3.133, 95%CI:1.677 ~ 14.495; OR _neutrality = 2.512, 95%CI:1.164 ~ 5.418) were more willing to recommend Non-EPI Vaccines. On the contrary, vaccination staff who believe that recommending Non-EPI vaccines increased their workload (OR _disagree = 0.307, 95%CI:0.11 ~ 0.856; OR _neutrality = 0.642, 95%CI:0.258 ~ 0.986) would decrease willingness to recommend them. The most of vaccination staff were willing to recommend non-EPI vaccines under major infectious disease outbreaks. To further control the pandemic of major infectious diseases, the health management departments should enhance the knowledge of vaccines among vaccination staff and alleviate their workload.

In countries in which rotavirus vaccines have been introduced for young infants, the incidence of rotavirus infections has dramatically decreased. This report presents an outbreak of rotavirus gastroenteritis among travelers. Data regarding the long-term protective effect of rotavirus vaccines after years of vaccination are scarce. A Japanese group of 14 children and nine adults traveled to Malaysia over 4 weeks. During travel, 15 of 23 patients developed gastroenteritis symptoms (Figure 1). Stool samples were collected from two symptomatic patients that tested positive for rotavirus. None of the five members with a history of rotavirus gastroenteritis developed symptoms. Nine of the 10 vaccinated children developed symptoms of acute gastroenteritis without the need for hospitalization. The only child without a history of vaccination or infection developed acute gastroenteritis and required hospitalization for continuous intravenous hydration. While individuals with a history of infection did not develop acute gastroenteritis, the protective effects of vaccination against symptomatic infection did not sustain long. This indicates the potential need for a booster dose of the rotavirus vaccine for travelers to rotavirus-endemic countries.

This study evaluated pneumococcal vaccination status using evaluable data collected from 445 of 1,313 managing directors of elderly care facilities in Japan through an online survey (September 5, 2022-November 25, 2022; UMIN000048747); comparisons were made with the influenza (2021-2022 vaccination only) and coronavirus disease 2019 (COVID-19) vaccination status. Among facilities who kept pneumococcal vaccination records (n = 42), the mean pneumococcal vaccination rate was 31.1%, with the rate being higher for the influenza (93.1%; n = 234) and COVID-19 (94.3%; n = 285) vaccines. Overall, excluding facilities that answered that the corresponding vaccine status at their sites was unknown, the percentage of facilities with high vaccination rates (80% to 100%) was substantially higher for the influenza (80.5%; 351/436) and COVID-19 (89.6%; 396/442) vaccines than for the pneumococcal vaccine (6.5%; 24/370). Multivariable analysis showed that major factors associated with a high pneumococcal vaccination rate (≥15%) were "managing director's willingness to recommend" and "pneumococcal vaccination request from the residents." The most common reason for their willingness to recommend the pneumococcal vaccine was that it is an effective disease prevention strategy (83.3%; 65/78) and for their unwillingness to recommend the pneumococcal vaccine was the inability to understand the effectiveness of the vaccine (43.6%; 17/39). In conclusion, there is a need to improve pneumococcal vaccination rates in elderly care facilities in Japan. Strategies such as increasing awareness and encouraging pneumococcal vaccine recommendation among managing directors, especially for residents not eligible for the national subsidy program, and providing regular training on the pneumococcal vaccine for staff and residents are required.

As the population ages, herpes zoster (HZ) and postherpetic neuralgia, which are associated with a substantial disease burden, are expected to increase. Ningbo began to implement the Vaccination Prescription Program for community individuals in April 2022. The anonymized HZ vaccination records of individuals aged above 50 during 2020-2023 were extracted from the Ningbo Immunization Information Management System. We applied interrupted time series analyses controlling for long-term trends and seasonality to assess the effects of the program on HZ vaccination coverage. Effect modification from demographic characteristics was investigated. Totally 18,133 doses of the HZ vaccine were administered. The cumulative coverage increased from 0.16‰ to 2.97‰, and the full series cumulative coverage from 0.04‰ to 2.48‰. Relatively higher coverage and full series coverage were observed among residents, females, individuals residing in inner districts and high socioeconomic regions, and those aged 50-59 years. During the transition period, a 468.7% increase in HZ vaccination coverage was evident (Rate Ratio [RR], 5.687; 95% Confidence Interval [CI], 2.334-13.857), and significant impact was detected among all demographic characteristics. During the post-implementation period, a 261.3% increase in coverage was evident (RR, 3.613; 95% CI, 1.202-10.858), while no effect was found among migrants, individuals living in regions with high socioeconomic status, and those aged above 70 years. Although the positive effect of the program, it is imperative to implement key strategies for providing affordable HZ vaccines, such as government funding, subsidies, and vaccination prescriptions from healthcare professionals, alongside peer initiatives and family members' education.

The constant mutation of SARS-CoV-2 has led to the continuous appearance of viral variants and their pandemics and has improved the development of vaccines with a broad spectrum of antigens to curb the spread of the virus. The work described here suggested a novel vaccine with a virus-like structure (VLS) composed of combined mRNA and protein that is capable of stimulating the immune system in a manner similar to that of viral infection. This VLS vaccine is characterized by its ability to specifically target dendritic cells and/or macrophages through S1 protein recognition of the DC-SIGN receptor in cells, which leads to direct mRNA delivery to these innate immune cells for activation of robust immunity with a broad spectrum of neutralizing antibodies and immune protective capacity against variants. Research on its composition characteristics and structural features has suggested its druggability. Compared with the current mRNA vaccine, the VLS vaccine was identified as having no cytotoxicity at its effective application dosage, while the results of safety observations in animals revealed fewer adverse reactions during immunization.

The World Health Organization (WHO) has recently declared another global health emergency due to the rapidly spreading monkeypox (Mpox) outbreak in numerous African countries. To address the unmet need to contain the outbreak using the existing vaccines, this study developed a lyophilization process for an effective, scalable and affordable Mpox mRNA-LNP vaccine candidate to address the global health crisis. A comprehensive evaluation and optimization of the vaccine formulation (the type/concentration of cryoprotectants, the type/concentration of buffer system, as well as the mRNA concentration and reconstitution solvent) and the freeze-drying process parameters (freezing method, temperature, cooling rate and primary/secondary drying conditions) were conducted. The freeze-dried product exhibits a uniform appearance and a moisture content of less than 1%. Reconstitution of the lyophilized mRNA-LNP resulted in equivalent particle size/polydispersity index, encapsulation efficiency and mRNA integrity compared to that of freshly prepared mRNA-LNP. Furthermore, the lyophilization process can be scaled up 100-fold to 2000 vials/batch. Notably, the lyophilized mRNA-LNP demonstrated a storage stability of at least 12 months at 4°C, and at ambient temperature for a minimum of 8 h post-reconstitution, exhibiting minimal deterioration in product quality. The in vitro biological activity and in vivo immunogenicity of the lyophilized mRNA-LNP was comparable to that of the freshly prepared mRNA-LNP. These results provide a compelling rationale for the utilization of lyophilization technology in enhancing the accessibility of the Mpox mRNA vaccine in developing countries, a strategy that is crucial for containing the global epidemic of Mpox infection.

The introduction of a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) into the Mexican pediatric national immunization program (NIP) has substantially reduced the burden of pneumococcal disease (PD) since 2010. This study aimed to estimate the impact of replacing either PCV13 or 15valent PCV (PCV15) with 20-valent PCV (PCV20) in the Mexican pediatric NIP. A decision-analytic Markov model was developed to compare the cost-effectiveness of PCV20 versus lower-valent vaccines from a Mexican public health sector (payer) perspective over 10 years. Epidemiological and cost inputs were sourced from Mexican data. Direct and indirect vaccine effects were estimated using PCV13 clinical effectiveness, 7-valent PCV efficacy studies, and PCV13 impact data in Mexico. The estimated disease and cost impact of PCV20 was compared with PCV13 and PCV15, all under a 2 + 1 dosing schedule. A discount rate of 5% per annum was applied to costs and health outcomes. Model robustness was evaluated through sensitivity analyses, including deterministic sensitivity analysis (DSA), probabilistic sensitivity analysis (PSA), and additional scenario assessments. PCV20 was estimated to provide considerably more health benefits than both comparators by averting more cases of PD compared with both PCV13 and PCV15, as well as a total cost saving of over 10 billion Mexican pesos. The DSA, PSA, and scenario assessments confirmed minimal deviation from the base case. Therefore, the introduction of PCV20 (2 + 1) into the Mexican pediatric NIP is expected to reduce the burden of PD and medical costs compared with lower-valent alternatives.

Despite the implementation of a single-dose universal varicella vaccination program in Peru since 2018, vaccination coverage rates (VCRs) remain low, with a VCR of 66% as of 2022. We employed a dynamic transmission model (DTM) to evaluate the impact of increasing varicella VCRs in Peru. We parameterized a previously published DTM with publicly available demographic, healthcare resource use, cost, and epidemiological data inputs specific to Peru (or suitable regional proxy), including Peruvian varicella VCRs up to 2022. We modeled six single-dose UVV strategies over 10 years (2023-2032) that increased VCRs to 80-90% over 1-, 2- or 5-year periods, compared with the reference strategy assuming the continuation of the current VCR of 65.6%. Clinical and economic outcomes were reported; economic outcomes were reported in 2023 USD with 5% annual discounting. Parameter uncertainty was evaluated through probabilistic and deterministic sensitivity analyses. All six strategies with increased VCR resulted in 13%-25% fewer varicella cases, and 13%-24% fewer outpatient and inpatient cases, over 10 years, compared to continuing the current varicella VCR, with shorter VCR ramp-up periods resulting in more clinical outcomes averted. However, this led to a 12%-21% ($0.05-0.08 per person per year) increase in costs from the payer perspective. The PSA indicated that model results were robust to parameter uncertainty. Increasing varicella VCR led to improved clinical outcomes, with small increase in costs. Improving VCR at faster rates leads to better clinical outcomes relative to the reference strategy at a small per-capita cost increase.

The dissemination of tumor cells with ensuing metastasis is responsible for most cancer-related deaths. Cancer vaccines may, by inducing tumor-specific effector T cells, offer a strategy to eliminate metastasizing tumor cells. However, several obstacles remain in the development of effective cancer vaccines, including the identification of adjuvants that enhance the evolvement and efficacy of tumor-specific T cells. Cholera toxin-based adjuvants have shown efficacy in vaccines for infectious diseases, but their role in cancer vaccine therapies remains to be elucidated. Here, we explored the potential of cholera toxin A1 (CTA1)-based adjuvants to boost anti-tumor T cell responses and protect against metastasis. We report that an adjuvant where CTA1 was fused to a dimer from Staphylococcus aureus protein A (DD) enhanced immune responses against the tumor-associated antigens TRP2 and Twist1 in mice, providing protection against B16F1 melanoma and 4T1 breast cancer metastasis, respectively. Both mucosal (intranasal) and systemic (intraperitoneal) vaccine administration provided effective protection against intravenously injected tumor cells, with intranasal administration leading to superior induction of CD4⁺ T cells at metastatic sites. When comparing antigens admixed with CTA1-DD to those fused with a CTA1-based adjuvant, the fusion construct elicited the strongest immunogenicity. Nevertheless, by administrating a 20-fold higher antigen dose also the admix formulation provided efficient protection against metastasis.