Expert Review of Vaccines最新文献

Introduction: Lyme disease is caused by the tick-borne spirochete pathogen Borrelia burgdorferi sensu lato (s.l.). Outer surface protein A (OspA) is expressed by B. burgdorferi s.l. while in the tick and antibodies against OspA introduced into the tick with the bloodmeal can prevent transmission. OspA-based vaccines have been validated in people, however, there are currently no available human Lyme disease vaccines. Hexavalent OspA vaccine VLA15 is designed to cover the dominant B. burgdorferi s.l. genospecies causing disease in North America and Europe and is currently the most advanced candidate human Lyme disease vaccine in clinical development.

Areas covered: A historical retrospective of the discovery and evolving burden of Lyme disease is covered, as well as relevant aspects of the vector biology, preclinical research underpinning development of VLA15, and its clinical development to date.

Expert opinion: Lyme disease has expanded over the past two decades in both incidence and geographic footprint and is anticipated to continue to increase in the future due to changing climate and human encroachment into wildlife areas. VLA15 is currently in the last stage of clinical development, and if found to be safe and efficacious, may offer an important prophylactic modality for prevention of Lyme disease.

Introduction: Prophylactic human papillomavirus vaccines have been in use in populations worldwide for nearly 20 years. Much has been learnt in relation to their effectiveness, safety, and how best to effectively implement them in populations to prevent cancer and other HPV-related diseases. Global challenges such as limited supply and the mismatch between those who can afford them and those with the greatest disease burden from cervical cancer have prevented optimal usage to date.

Areas covered: Here we identified recent papers and focus upon the accumulated evidence regarding HPV vaccine: i) effectiveness in preventing cancer and precancerous lesions, ii) safety in population usage, iii) trial evidence supporting registration of four newer vaccines, iv) progress in country-level introductions and coverage, and v) lessons learned in effective implementation.

Expert opinion: Reasons for optimism are many, with vast cumulative knowledge on impact, safety and implementation and accelerating HPV vaccine introductions, simplification of delivery and reduced costs through single dose approaches and supply constraints easing. However, considerable challenges remain in achieving and maintaining high and equitable global coverage, given the uncertainty in funding, risk to ongoing prioritization of health equity and to vaccine confidence in the current global public health environment.

Background: Herpes zoster (HZ), caused by varicella-zoster virus, primarily affects the elderly. In May 2023, the first domestically produced live attenuated zoster vaccine was approved for use in adults aged 40 years or older in China.

Research design and methods: We conducted a self-controlled case series study to collect hospitalization events among 25,000 vaccinated adults (April 2020-December 2023, 5 regions) during the risk period (0-42 days) and the control period (72-162 days). Conditional Poisson regression models and conditional logistic regression models were applied to compare the risk of hospitalization.

Results: The rate ratio of hospitalization following immunization was 0·381 (0·323-0·450). Compared with those in control period, the incidence rates of the following hospitalization events decreased: RRs of 0·297 (0·203-0·435) for stroke, cerebrovascular, and nervous system diseases; 0·296 (0·205-0·527) for cardiovascular diseases; 0·183 (0·054-0·627) for genitourinary system diseases; 0·246 (0·155-0·391) for respiratory, thoracic, and mediastinal diseases; 0·238 (0·089-0·635) for diseases of eye and adnexal diseases; and 0·202 (0·053-0·766) for skin and subcutaneous tissue diseases.

Conclusions: This study confirms the safety of the live attenuated zoster vaccine, demonstrating that vaccination does not increase the risk of hospitalization and may even reduce the incidence of hospitalization.

Background: To compare the adherence and efficacy between the 0 - 7 - 21-day and the 0 - 1 - 6-month hepatitis B virus (HBV) vaccination schedules among people who use drugs (PWUD) in China.

Research design and methods: A randomized controlled trial was conducted in 1261 HBV-susceptible PWUD from compulsory isolated detoxification centers (CIDCs) and methadone maintenance treatment (MMT) clinics in Xi'an. A 20 µg per-dose vaccine was used. HBV surface antibody (anti-HBs), surface antigen, and core antibody were tested at months 7, 15, and 22 after the first dose.

Results: Third-dose coverage was significantly higher in the 0 - 7 - 21-day group (74.40%) than in the 0 - 1 - 6-month group (51.58%, p < 0.001), mainly driven by participants from CIDCs (77.75% vs. 45.69%). Anti-HBs positive rates at months 7, 15, and 22 among participants who completed all three doses were significantly higher for the 0 - 1 - 6-month schedule (90.71%, 76.82%, and 67.35%) than for the 0 - 7 - 21-day schedule (74.23%, 49.40%, and 40.95%; all p < 0.001). HBV infection incidence was similar between schedules, but significantly different between vaccinees and non-vaccinees (p = 0.018).

Conclusions: The 0 - 7 - 21-day schedule substantially enhances three-dose completion in PWUD, but induces a notably weaker anti-HBs response and persistence. Schedules should be selected based on the management models for PWUD and their individual characteristics.

Clinical trial registration: Chinese Clinical Trial Registry (ChiCTR1900022403).

Background: This study analyzed the health and economic outcomes of the 21-valent pneumococcal conjugate vaccine (PNEU-C-21; CAPVAXIVE®) compared to either PNEU-C-20 or PNEU-P-23. Cohorts in the cost-effectiveness analyses included vaccine-naïve 57- and 65-year-olds and vaccine-experienced 70-year-olds.

Research design and methods: A published Markov model simulated the movement of the Canadian population among four health states: healthy, pneumococcal disease (invasive pneumococcal disease and community-acquired pneumonia attributed to S. pneumoniae), post-meningitis sequelae, and death. The model was populated with published literature and publicly available databases and/or reports. Model inputs included demographic data, epidemiologic data, serotype distribution, vaccine effectiveness, costs, and health-related utilities. The model used a lifetime horizon and 1.5% discounting of costs and life years. Key outcomes included the following: cases, deaths, costs, and incremental cost-effectiveness ratios.

Results: The PNEU-C-21 strategy prevented substantially more cases and deaths when compared to the PNEU-C-20 or PNEU-P-23 strategies. For both vaccine-naïve cohorts, the ICERs were dominant for both PNEU-C-21 vs. PNEU-C-20 and PNEU-C-21 vs. PNEU-P-23; among adults aged 70 years, previously vaccinated with PNEU-P-23, PNEU-C-21 was dominant over PNEU-C-20.

Conclusions: These results demonstrate that PNEU-C-21 can prevent a substantial number of cases and deaths while remaining highly cost-effective over a range of inputs and scenarios in Canada.

Introduction: Neonatal sepsis, a systemic infection occurring in infants within their first 28 days of life, is a leading cause of mortality globally. The burden is especially severe in low- and middle-income countries (LMICs), where incidence and mortality rates are higher than in high-resource settings. Antimicrobial resistance, driven by multidrug-resistant pathogens prevalent in LMICs, further complicates its effective management. Vaccination offers a promising strategy to prevent infections caused by common neonatal sepsis pathogens, potentially reducing sepsis incidence and mitigating resistance.

Area covered: This review examines the burden of bacterial pathogens, specifically Group B Streptococcus (GBS), Klebsiella pneumoniae, and Escherichia coli, responsible for neonatal sepsis, drawing from a comprehensive literature search focusing on the last ten years across major databases. It provides an overview of vaccine candidates in clinical development, highlights innovative approaches in preclinical research, and discusses the key challenges associated with vaccine strategies preventing neonatal sepsis.

Expert opinion: Given the multivalency of vaccines for neonatal sepsis, innovative technologies are under investigation. Defining correlate of protections has been critical for GBS vaccine development, and may pave the way for vaccines against K. pneumoniae and E. coli. Novel regulatory and clinical strategies, including disease-based rather than pathogen-specific approaches, should be explored.

Background: The role of Fc-mediated immune responses in protecting against herpes zoster remains poorly understood. This study aimed to evaluate the Fc-mediated immune responses of anti-VZV glycoprotein E antibodies induced by two licensed varicella-zoster virus vaccines.

Research design and methods: We established two cohorts, each consisting of 48 healthy participants aged 50 or above, who received either the ZVL or RZV. Serum samples were measured to evaluate the Fc-mediated immune responses for antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent neutrophil phagocytosis (ADNP) against VZV-gE. The correlations between Fc-mediated functions and the IgG levels were also analyzed.

Results: Both ZVL and RZV significantly induced Fc effector function responses against HZ in participants after vaccination. Compared with ZVL recipients, RZV recipients exhibited significantly higher increase-fold of ADCC responses (ZVL: 1.93-fold; RZV: 8.44-fold, p < 0.001). In each vaccine group, the younger recipients showed higher ADCC responses than did the older (ZVL: 2.17-fold vs. 1.45-fold, p = 0.0136; RZV: 8.93-fold vs. 7.43-fold, p = 0.0677). Similar patterns were observed for ADCP and ADNP responses.

Conclusion: RZV induced superior Fc effector functions of VZV-gE antibodies compared to ZVL did. Older adults exhibited weaker Fc-mediated responses compared to younger adults following vaccination.

Introduction: Pneumococcal disease leads to high morbidity and mortality, particularly in older adults and immunocompromised individuals. Many pneumococcal conjugated vaccines (PCVs) have become available. However, the immunogenicity, efficacy, and effectiveness data of these vaccines in older adults and immunocompromised individuals are limited.

Areas covered: This review aims to critically examine the immune responses, immune correlations, efficacy, real-world effectiveness, and cost-effectiveness of pneumococcal conjugated vaccines (PCVs) in older adults and immunocompromised individuals.

Expert opinion: A single dose of 20-valent or 21-valent PCV is recommended for older adults and immunocompromised individuals. Immune correlates of protection vary by serotype and race. An IgG level of 0.35 µg/mL is associated with protection, though this threshold is serotype-dependent. Opsonophagocytic assays, with a threshold of 1:8, remain the most reliable functional correlate of protection against invasive pneumococcal disease. Standardized immunological assays are essential for evaluating immune responses. High-valent PCVs have shown noninferior immunogenicity compared to PCV13, though geometric mean fold rises (GMFRs) for shared serotypes are slightly lower. Real-world effectiveness data are still needed, particularly in regions with differing serotype prevalence. Serotype surveillance is crucial when introducing PCV programs. Due to the high cost of higher-valent PCVs, many countries continue using PCV13 or PCV15 followed by PPSV23 for high-risk groups.

Background: Significant residual burden of invasive pneumococcal disease (IPD) is attributable to Streptococcus pneumoniae serotypes not included in any available vaccines in Germany. This study quantified the burden of invasive pneumococcal disease attributable to PCV21 and PCV20 serotypes among German adults.

Research design and methods: A published state-transition Markov model estimated the lifetime cases, deaths, and direct costs (2023 Euros) of IPD by age (18-49, 50-59, and 60 years and older) and risk group (low-risk, at-risk, and high-risk) in Germany. One-way sensitivity analysis on PCV21 cost was conducted.

Results: Across all age groups, there were 50,462 more IPD cases and 8895 deaths attributable to the serotypes in PCV21 compared to PCV20. The eight unique serotypes to PCV21 accounted for approximately 22% of disease. Higher direct costs were associated with PCV21 serotypes versus PCV20 serotypes (€505,094,685 versus €389,835,550, respectively). Discount rate of costs was the most influential input.

Conclusions: Serotypes in PCV21 compared to PCV20 are associated with greater health and economic burden in Germany, primarily driven by the eight unique serotypes included in PCV21 and no other licensed vaccine. Including PCV21 in the national German vaccination guidelines may substantially reduce IPD-related health and economic burden among adults.