Expert Review of Vaccines最新文献

Introduction: This review provides an expert perspective on the sustained value of seasonal influenza vaccines as they transition from quadrivalent to trivalent formulations, based on apparent elimination of the B/Yamagata strain from circulation and subsequent advice from the World Health Organization (WHO) to remove the B/Yamagata antigen from influenza vaccines. Influenza has a high clinical and economic burden globally. However, coronavirus disease 2019 has created new challenges for managing seasonal influenza by amplifying vaccine hesitancy. Understanding why influenza virus circulation is monitored and vaccines subsequently updated is important for all relevant stakeholders to maintain confidence in the value of seasonal influenza vaccination.

Areas covered: Discussion is provided on the dynamic nature of communicable diseases, influenza virus monitoring and WHO vaccine composition guidance, and maintaining the value of influenza vaccination to individuals, society, and healthcare systems.

Expert opinion: The move from quadrivalent to trivalent influenza vaccines is a result of findings from strain surveillance. Continued surveillance and targeting of vaccines against strains most commonly in circulation to keep effectiveness high, and ensure the highest value of vaccination is vital to prevent influenza infection and severe illness, thus reducing pressure on healthcare systems and reducing the economic impact of influenza outbreaks.

Background: Respiratory syncytial virus (RSV) can cause acute respiratory infection (ARI) and severe symptoms in adults ≥60 years. The adjuvanted RSV prefusion F protein vaccine (adjuvanted RSVPreF3) offers protection to adults against RSV ARI and RSV lower respiratory tract disease (LRTD). We modeled the burden of RSV among adults ≥60 years in India and Southeast Asia, and the potential impact of RSV vaccination.

Methods: A Markov model was adapted to the settings of India, Indonesia, Malaysia, the Philippines, Thailand, and Vietnam. RSV ARI cases, LRTD-associated hospitalizations, pneumonia, and deaths were tallied over a five-year period. Impact of adjuvanted RSVPreF3 vaccination with 30% and 70% coverage was assessed by calculation of incremental differences versus no vaccination.

Results: A total of 73.9 million RSV ARI were projected to occur in adults ≥60 years living in the selected countries. Numbers of hospitalizations, pneumonia, and deaths were approximately 3.1 million, 2.9 million, and 294,000, respectively. Adjuvanted RSVPreF3 vaccination with a 30% coverage could prevent 8.6 million RSV ARI, 460,255 hospitalizations, 423,659 pneumonia, and 43,693 deaths over 5 years.

Conclusions: The projected burden of RSV was substantial in India and Southeast Asia, and could greatly be alleviated through adjuvanted RSVPreF3 vaccination of adults ≥60 years.

Background: The potential occurrence of autoimmune- and pregnancy-related adverse events with the quadrivalent human papillomavirus (4vHPV) vaccine has previously not been assessed in the real-world setting in China.

Research design and methods: A retrospective active post-marketing surveillance of the 4vHPV vaccine has been conducted among Chinese women aged 20-45 years between January 2018 and March 2021 in the Ningbo city. Incidences of seven pre-specified autoimmune diseases diagnosed within 6 months after the 4vHPV vaccination were calculated. Cases of stillbirth and 23 congenital anomalies diagnosed within 3 months from birth in infants were collected in women with maternal exposure to the 4vHPV vaccine.

Results: A total of 195,593 doses of the 4vHPV vaccine were administered to 76,212 women. New-onset cases of autoimmune diseases were diagnosed in 113 women, comprising 71 cases of Hashimoto's disease (130.84/100,000 person-years), 24 cases of Graves' disease (44.21/100,000 person-years), 1 case of optic neuritis (1.84/100,000 person-years), and 17 cases of uveitis (31.31/100,000 person-years). Among the 168 women with maternal exposure to the 4vHPV vaccine, five cases of congenital heart disease were observed in their infants.

Conclusions: These findings confirm the favorable benefit/risk profile of the 4vHPV vaccine in Chinese women in the routine healthcare setting.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI; RSV-LRTI) among infants in Chile; young infants and infants born prematurely are at greatest risk.

Research design and methods: A cohort model was developed to evaluate cost-effectiveness of strategies preventing RSV-LRTI in infants. Using the model, we calculated the economically justifiable price (EJP) of maternal RSVpreF vaccination (MV) versus no intervention and then evaluated the cost-effectiveness of MV (cost/dose assumed at EJP) with complementary use of monoclonal antibody nirsevimab for unprotected infants (MV+N) versus nirsevimab alone (NA) to prevent RSV-LRTI. Nirsevimab published price was $260.00; costs/prices reported in 2023 US$.

Results: NA yielded 20,247 cases (hospital: 3,773, emergency ward: 16,474) and $57.2 million (M) in total costs (medical: $6.3 M, intervention: $48.7 M, indirect: $2.2 M). MV+N yielded 23,906 cases (hospital: 3,137, emergency ward: 20,769) and $28.7 M in costs (medical: $4.8 M, intervention: $21.7 M [RSVpreF assumed $75.77/dose; nirsevimab procured $260.00/dose], indirect: $2.2 M). With costs lower by $28.4 M and increased quality-adjusted life-years, MV+N would be cost-saving versus NA.

Conclusions: RSVpreF vaccination among pregnant women along with nirsevimab for unprotected infants in Chile would be the most efficient use of resources, yielding substantial cost savings compared to use of nirsevimab alone.

Introduction: Seasonal influenza causes up to 50 million symptomatic cases and 15,000 - 70,000 deaths annually within the European Union. While influenza affects all age groups, adults aged ≥65 years disproportionately experience high rates of influenza-related hospitalizations and complications. Vaccination remains the cornerstone of influenza prevention and the most effective intervention for reducing morbidity and mortality.

Area covered: This review focuses on the high-dose inactivated influenza vaccine, an enhanced formulation recommended for the immunization of adults aged 60/65 and older. The high dose vaccine contains four times the hemagglutinin antigen compared to the standard dose vaccine, resulting in significantly higher and more sustained antibody responses. This increased immunogenicity is especially pronounced in adults aged ≥75 years and in those with cardiopulmonary diseases or immunocompromised states.

Expert opinion: Expanding the use of the high-dose vaccine to adults aged 50-64 years may proactively address immunosenescence and enhance protection in this population. Moreover, the development of multicomponent vaccines targeting both influenza and COVID-19 within a single formulation could enhance vaccine uptake and streamline immunization programs. Ultimately, the high-dose vaccine has the potential to replace the standard-dose formulation in older adults, thereby optimizing influenza prevention and reducing disease burden.

Background: The tetravalent dengue vaccine TAK-003 is contraindicated during pregnancy. Pregnant women were excluded from TAK-003 clinical studies; however, some pregnancies occurred unintentionally.

Research design and methods: This post-hoc analysis of phase 2 and 3 studies, evaluated pregnancy outcomes and neonatal adverse events (AEs) following unintentional vaccination during the time period ('exposure window') when women could be pregnant (within 44 days before last menstrual period until the outcome of pregnancy).

Results: Of the 557 reported pregnancies, 38 (TAK-003, n = 28/375; placebo, n = 10/182) occurred inside the exposure window. Of these, 28 (TAK-003, n = 23; placebo, n = 5) resulted in live births, four resulted in elective terminations (TAK-003, n = 2; placebo, n = 2), five in spontaneous abortions (TAK-003, n = 3; placebo, n = 2) and one unknown outcome (placebo).Of the spontaneous abortions, there was no significant difference between TAK-003 and placebo recipients, or between those occurring within or outside the exposure window. Six participants who received TAK-003 in the exposure window and two neonates experienced serious AEs; none were considered TAK-003 related.

Conclusions: This post-hoc analysis found no evidence of increased adverse pregnancy outcomes following unintentional TAK-003 vaccination occurring inside the exposure window compared with placebo.

Clinical trial registration: The clinical trials from which data were extracted are registered at www.clinicaltrials.gov (identifiers are NCT02193087, NCT01511250, NCT02302066, NCT02425098, NCT03746015, NCT02747927, NCT03999996, NCT03423173, NCT03342898, NCT03771963, NCT04313244, NCT02948829, NCT035252119, NCT03341637).

Background: This study proposes the reverse cumulative distribution curve (RCDC) for optimal dose selection and a scaled logit model for estimating protection in EV71 vaccine development.

Research design and methods: Data were from a phase 2 trial involving infants and young children randomized to receive either 640 U with or without adjuvant, 320 U with adjuvant, 160 U with adjuvant EV71 vaccines, or placebo. RCDCs were constructed using neutralizing antibody titers 28 days post-vaccination. Robustness of RCDC parameters was assessed via coefficient of variation for the area under the curve (AUC), the relative optimal point, median on the curve, and antibody titer of the point of maximum curvature, with geometric mean titer (GMT) as control. The scaled logit model estimated protection against EV71-associated disease for the selected optimal dose.

Results: The AUC and relative optimal point demonstrated greater robustness than GMT. The 640 U with adjuvant dose had the highest AUC (0.64, 95% CI: 0.61-0.66), sum of coordinates of the relative optimal point (1.40, 95% CI: 1.34-1.43), and the highest estimated protection (93.36%, 95% CI: 79.91-97.86).

Conclusions: AUC and relative optimal point of RCDC are effective for early vaccine dose screening, with protection estimated by the scaled logit model.

Background: The burden of pneumococcal disease varies regionally in China, disproportionately affecting children in many provinces such as Qinghai and Hainan. Nevertheless, the absence of a pneumococcal conjugate vaccine (PCV) in the National Immunization Program (NIP) or local programs presents limited coverage. This study evaluated the health and economic impact of including PCV in immunization programs in Qinghai and Hainan.

Research design and methods: A decision tree Markov model was constructed to simulate health outcomes and lifetime costs among children under different 13-valent PCV (PCV13) vaccination strategies compared to current practices, from societal and healthcare perspectives. Data on epidemiology, vaccine efficacy, cost, and utility were obtained from the literature and open databases. Sensitivity analyses were conducted to explore parameter uncertainty.

Results: Including three-dose PCV13 in provincial programs at NIP coverage (98.91%) could avert 7100 episodes and 118 deaths in Qinghai, and 6200 episodes and 66 deaths in Hainan. It was cost-effective at the $68.2/dose in private market and cost-saving at the United Nations Children's Fund (UNICEF) recommended $25/dose for both provinces. Increasing coverage to 50% or 75% was also cost-effective. Sensitivity analyses confirmed the robustness of the results despite parameter uncertainty.

Conclusions: Prioritizing PCV13 in immunization programs in Qinghai and Hainan could effectively reduce disease burden, improve population health, and promote health equity.

Introduction: Vaccines save lives. They are integral to reducing the morbidity and mortality of vaccine-preventable infections in solid organ transplant recipients. Pre-transplant vaccination provides a unique opportunity for administration of live, viral vaccines, and enhanced vaccine efficacy, compared to the post-transplant period with decreased vaccine response due to immunosuppression.

Areas covered: We discuss a general approach to pre- and post-transplant vaccination in solid organ transplant candidates and recipients. We then review guideline statements and recent literature related to individual vaccines, including the recently developed respiratory syncytial virus vaccine. Travel and occupation-related vaccines are also discussed.

Expert opinion: The challenge of vaccination for immunocompromised patients expands as the prevalence of immunocompromised adults rises, and immunocompromised patients are frequently excluded from vaccine trials. In an age of vaccine hesitancy and reemerging vaccine-preventable infections, well-powered, prospective studies are needed to evaluate the clinical effectiveness of vaccines in solid organ transplant candidates and recipients.