Andrea Schilling

This second part of this expert panel review explores the broader impact of vaccines across the lifespan, emphasizing their role beyond immediate infection control. Vaccines not only extend life expectancy but also influence long-term health trajectories, particularly during the critical first 1000 days of life, where they prevent severe infections, disability, and mortality. They contribute to cancer prevention through vaccination against human papillomavirus and hepatitis B, reduce cardiovascular events and complications in individuals with chronic diseases, and protect against late-life functional decline. Furthermore, vaccines exert lasting effects on healthy aging by modulating inflammation and preserving independence, while proposed vaccination schemes illustrate the need for a comprehensive, life-course approach. Together with Part 1, which focused on immunosenescence and immune modulation, this closing installment underscores vaccination as a cornerstone of sustainable health policy, reinforcing its pivotal role in extending both lifespan and healthspan for future generations.

Population aging is the most significant demographic transformation of the 21st century, reshaping health systems, economies, and societies. The biological processes of immunosenescence and inflammaging weaken host defenses, reduce vaccine effectiveness, and increase vulnerability to infectious and chronic diseases. These changes underscore the urgent need for preventive strategies that extend beyond childhood immunization. Vaccination is a cornerstone of healthy aging, capable of preventing infections and has been associated with reductions in systemic inflammation, frailty, and loss of functional independence in later life. Furthermore, new insights into vaccine-mediated immunomodulation, including trained immunity, adjuvanted formulations, and epigenetic reprogramming, highlight the evolving role of vaccines as modulators of immune fitness across the lifespan. This first part of our review examines the intersection of aging and immunity, as well as the potential of vaccines to address these challenges. Part 2 will expand on specific vaccines, proposed vaccination schedules, and global perspectives for lifelong immunization.

Population aging is the most significant demographic transformation of the 21st century, reshaping health systems, economies, and societies. The biological processes of immunosenescence and inflammaging weaken host defenses, reduce vaccine effectiveness, and increase vulnerability to infectious and chronic diseases. These changes underscore the urgent need for preventive strategies that extend beyond childhood immunization. Vaccination is a cornerstone of healthy aging, capable of preventing infections and has been associated with reductions in systemic inflammation, frailty, and loss of functional independence in later life. Furthermore, new insights into vaccine-mediated immunomodulation, including trained immunity, adjuvanted formulations, and epigenetic reprogramming, highlight the evolving role of vaccines as modulators of immune fitness across the lifespan. This first part of our review examines the intersection of aging and immunity, as well as the potential of vaccines to address these challenges. Part 2 will expand on specific vaccines, proposed vaccination schedules, and global perspectives for lifelong immunization.

This second part of the expert panel review explores the broader impact of vaccines across the lifespan, emphasizing their role beyond immediate infection control. Vaccines not only extend life expectancy but also influence long-term health trajectories, particularly during the critical first 1000 days of life, where they prevent severe infections, disability, and mortality. They contribute to cancer prevention through immunization against human papillomavirus and hepatitis B, reduce cardiovascular events and complications in individuals with chronic diseases, and protect against late-life functional decline. Furthermore, vaccines exert lasting effects on healthy aging by modulating inflammation and preserving independence, while proposed immunization schemes illustrate the need for a comprehensive, life-course approach. Together with Part 1, which focused on immunosenescence and immune modulation, this closing installment underscores vaccination as a cornerstone of sustainable health policy, reinforcing its pivotal role in extending both lifespan and healthspan for future generations.

Annual vaccination is an effective strategy for preventing severe disease caused by seasonal influenza. Quadrivalent influenza vaccines (QIVs) protect against two strains of influenza A and two strains of influenza B, thereby enhancing the host antiviral neutralizing antibody response and inducing CD4⁺ and CD8⁺ T cell responses. Here, we report findings from a randomized, double-blind, active-controlled phase 3 clinical trial (NCT05431725) that includes 334 healthy adults aged 18–64 years and evaluates the humoral and cellular antiviral immune responses induced by two inactivated QIVs, Sinovac-QIV and Vaxigrip-Tetra™. The primary endpoint of the study is the specific antibody responses measured by hemagglutination inhibition (HAI) assays 28 days post-vaccination, while the secondary endpoint is virus-specific T cell responses. Both QIVs elicit significant increases in antibody titers 28 days after vaccination; Sinovac-QIV induces 9–10-fold increases in geometric mean titers, while Vaxigrip-Tetra™ elicits 7–8-fold increases (p < 0.05). Cellular immune responses using ELISPOT and supervised and unsupervised flow cytometry analyses show that both vaccines modulate the frequency of hemagglutinin-specific CD4⁺ and CD8⁺ T cell subsets, inducing distinct T cell response profiles. Although cellular analyses are evaluated in a subgroup of the cohort, the data indicate that both QIVs induce robust humoral and cellular immunity in adults, providing mechanistic insights into vaccine-induced protection.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac^® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac^®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac^® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

In 2006, the human papillomavirus (HPV) vaccine was approved for use as an effective intervention for reducing the risk of developing cervical cancer; however, its successful implementation is dependent on acceptability. This study aims to provide a comprehensive understanding of the reasons that favor or do not favor the acceptability of HPV vaccines. Methods: We conducted a systematic review and meta-summary of qualitative research on 16 databases. A total of 32 articles that considered the perspectives of vaccine users, their parents, and the professionals who care for them were reviewed. Synthesis was conducted as described by Sandelowski and Barroso. Results: We used inductive and deductive methods to obtain a total of 22 dimensions, out of which three issues stood out that should be considered to improve acceptability and are formed by three groups of study, namely, information about the vaccine, fears and side effects, and sexuality associated with the vaccine. Conclusions: Acceptability, as well as adherence to HPV vaccination, is a complex concept. This review highlights the perspectives of the three sets of actors involved in the process (i.e., users, parents, and professionals) and views these factors in relation to acceptability as a guide for new interventions.

Background: High‐income country studies show unfavorable trends in stroke incidence (SI) in younger populations. We aimed to estimate temporal change in SI disaggregated by age and sex in Latin America and the Caribbean region. Methods and Results: A search strategy was used in MEDLINE, WOS, and LILACS databases from 1997 to 2021, including prospective population‐based observational studies with first‐ever stroke incidence in Latin America. Reports without data broken down by age and sex were excluded. Risk of bias was assessed with The Joanna Briggs Institute's guide. The main outcomes were incidence rate ratio and relative temporal trend ratio of SI, comparing time periods before 2010 with after 2010. Pooled relative temporal trend ratios considering only studies with 2 periods in the same population were calculated by random‐effects meta‐analysis. Meta‐regression analysis was used to evaluate incidence rate determinants. From 9242 records identified, 6 studies were selected including 4483 first‐ever stroke in 4 101 084 individuals. Crude incidence rate ratio in younger subjects (P for heterogeneity <0.001). Conclusions: An unfavorable change in SI in young people, especially in women, was detected in population‐based studies in the past decade in Latin America and the Caribbean. Further investigation of the explanatory variables is required to ameliorate stroke prevention and inform local decision‐makers. Registration: URL: https://www.crd.york.ac.uk/prospero/ Identifier: CRD42022332563.

Background High-income countries studies show unfavorable trends in stroke incidence (SI) in younger populations. We aimed to estimate temporal change in SI disaggregated by age and sex in Latin America and the Caribbean region (LAC). Methods A search strategy was used in MEDLINE, WOS, and LILACS databases from 1997 to 2021, including prospective observational studies with age and sex-disaggregated data of first-ever stroke (FES) incidence. Risk of bias was assessed with The Joanna Briggs Institute’s guide. The main outcomes were incidence rate ratio (IRR) and relative temporal trend ratio (RTTR) of SI, comparing time periods ≥2010 with Results From 9,242 records identified, six studies were selected including 4,483 FES in 4,101,084 individuals. Crude IRR in younger subjects (Conclusions An unfavorable change in SI in young people - especially in women - was detected in the last decade in LAC. Further investigation of the explanatory variables is required to ameliorate stroke prevention and inform local decision-makers. Registration of protocol CRD42022332563 (PROSPERO).

Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac^®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac^® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac^® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.