Vaccines

15 pages, 2562 KB

Open AccessArticle

A Ganoderma lucidum Polysaccharide-Modified Nanoadjuvant Elicits Potent Cellular Immunity for Hepatitis B Vaccine

by Zhe Zhai, Jiansong You and Xuhan Liu

Vaccines 2026, 14(9), 779; https://doi.org/10.3390/vaccines14090779 (registering DOI) - 6 Sep 2026

Background: Aluminum-adjuvanted hepatitis B vaccines effectively prevent primary HBV infection but predominantly favor humoral immunity and have limited capacity to induce strong cellular responses. To improve immune-response quality, we developed a Ganoderma lucidum polysaccharide-modified hybrid nanoparticle adjuvant (GHNP) for hepatitis B surface antigen [...] Read more.

Background: Aluminum-adjuvanted hepatitis B vaccines effectively prevent primary HBV infection but predominantly favor humoral immunity and have limited capacity to induce strong cellular responses. To improve immune-response quality, we developed a Ganoderma lucidum polysaccharide-modified hybrid nanoparticle adjuvant (GHNP) for hepatitis B surface antigen (HBsAg) vaccination. Methods: Cationic PEG-PCL/DOTAP hybrid nanoparticles (HNPs) were surface-modified with Ganoderma lucidum polysaccharide (GLP) at different mass ratios and characterized by particle size, polydispersity index, zeta potential, and transmission electron microscopy. Antigen uptake, RAW264.7 cell viability, MHC II expression, and TLR2/4-associated TNF-α secretion were evaluated in vitro. C57BL/6 mice were immunized intramuscularly with PBS, HBsAg, HBsAg + Aluminum, HBsAg@HNP, or HBsAg@GHNP6 on Days 0, 14, and 28. HBsAg-specific antibodies, splenocyte activation, proliferation, and cytokine secretion were assessed. Results: GHNP6 showed suitable physicochemical properties, acceptable cytocompatibility at concentrations up to 10 μg·mL⁻¹, and efficient model-antigen uptake. GHNP increased MHC II expression in RAW264.7 cells, and TLR2/4 inhibition reduced nanoparticle-associated TNF-α secretion, supporting involvement of these pathways in immune activation. In vivo, HBsAg@GHNP6 induced robust HBsAg-specific IgG responses and a higher IgG2a/IgG1 ratio than HBsAg@HNP and HBsAg + Aluminum. It also produced the highest splenocyte proliferation after HBsAg restimulation, with lower IL-6 secretion than HBsAg + Aluminum and moderately increased IFN-γ compared with PBS and free HBsAg. Conclusions: GHNP integrates nanoparticle-assisted antigen delivery with GLP-mediated immunomodulation and represents a promising strategy for enhancing cellular immune responses while maintaining humoral immunity in HBsAg vaccination. Full article

(This article belongs to the Special Issue Novel Adjuvants and Delivery Technologies for Vaccine Development)

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18 pages, 973 KB

Open AccessSystematic Review

Evaluation of Adjuvant Administration of a Prophylactic HPV Vaccine in HPV-Positive Infertile Men: A Systematic Review

by Ana Banko, Ivana Lazarevic, Danijela Miljanovic, Marko Jankovic, Jovana Cupic and Andja Cirkovic

Vaccines 2026, 14(9), 778; https://doi.org/10.3390/vaccines14090778 (registering DOI) - 6 Sep 2026

Abstract

Background: Accumulating data suggest that human papillomavirus (HPV) infection may be associated with male infertility by impairing sperm quality. An induced anti-HPV humoral immune response could mediate the effective clearance of HPV infection. This systematic review aimed to assess reported differences in semen [...] Read more.

Background: Accumulating data suggest that human papillomavirus (HPV) infection may be associated with male infertility by impairing sperm quality. An induced anti-HPV humoral immune response could mediate the effective clearance of HPV infection. This systematic review aimed to assess reported differences in semen quality parameters and HPV presence in men with persistent HPV infection after adjuvant administration of a prophylactic HPV vaccine. Methods: Possibly eligible articles were retrieved from three electronic databases (PubMed, Scopus, and Web of Science) since 26 June 2026, with three ultimately included in both qualitative and quantitative analysis. Results: The estimated HPV DNA negativity was 74% (95% CI 59–86) and 98% (95% CI 78–100) at the end of vaccination and 6 months after complete vaccination. Conclusions: This study identified limited evidence suggesting a potential benefit of HPV vaccination in infertile HPV-positive men, particularly in terms of shift toward HPV negativity. Given the small number of available studies and their methodological limitations, further large, well-designed prospective trials are required to determine whether adjuvant administration of a prophylactic HPV vaccine provides clinically relevant benefits in this population. Full article

(This article belongs to the Special Issue Vaccines for the Vulnerable Population)

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17 pages, 732 KB

Open AccessSystematic Review

Guidelines on Immunization of People with Chronic Neurological Disorders: A Systematic Review

by Giuseppina Lo Moro, Andreea Mihaela Butnaru, Carola Toffanin, Anastasia Cataldo, Simona Mazzeo, Manuela Martella, Giacomo Scaioli, Fabrizio Bert and Roberta Siliquini

Vaccines 2026, 14(9), 777; https://doi.org/10.3390/vaccines14090777 (registering DOI) - 5 Sep 2026

Abstract

Background: People with chronic neurological disorders may be vulnerable to severe outcomes from vaccine-preventable infections. However, immunization recommendations for these patients may be difficult to identify and apply. This systematic review aimed to identify and describe official guidelines on preventive active immunization for [...] Read more.

Background: People with chronic neurological disorders may be vulnerable to severe outcomes from vaccine-preventable infections. However, immunization recommendations for these patients may be difficult to identify and apply. This systematic review aimed to identify and describe official guidelines on preventive active immunization for individuals with chronic neurological disorders. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 and registered in the PROSPERO International prospective register of systematic reviews (CRD420251005848). Bibliographic databases (PubMed, Embase, Scopus) and grey literature sources were searched to identify official national or international clinical practice guidelines or comparable structured guidance documents providing recommendations relevant to chronic neurological disorders. The search was restricted to countries with a Human Development Index greater than 0.8, to allow comparison across broadly comparable healthcare and socioeconomic contexts. Data were extracted on document characteristics, neurological conditions addressed, vaccines covered, and vaccination-related recommendations. Results: Overall, 12 unique documents were included. Four were vaccination-focused documents including recommendations for neurological disorders, four were disease-management guidelines including vaccination-related recommendations, and four specifically addressed vaccination in selected neurological diseases. Guidance was unevenly distributed across countries, neurological conditions, and document types. Influenza and COVID-19 vaccination were the most consistently addressed vaccines. Multiple sclerosis was the condition with the most detailed guidance, especially regarding vaccination before disease-modifying therapies, live attenuated vaccines, vaccine timing in relation to immunosuppression or relapse, and protection of close contacts. Conclusions: Official immunization guidance for people with chronic neurological disorders remains limited and heterogeneous. Future guidelines should provide clearer and regularly updated recommendations to support vaccination assessment, treatment-sensitive planning, and multidisciplinary coordination. Full article

(This article belongs to the Special Issue Vaccines for the Vulnerable Population)

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Graphical abstract

18 pages, 681 KB

Open AccessArticle

Utilizing the CFIR to Evaluate Rural COVID-19 Vaccine Uptake: Extension Personnel Perspectives

by Megan Undeberg, Ghazal Meratnia, Skylar Zelenko and Kimberly McKeirnan

Vaccines 2026, 14(9), 776; https://doi.org/10.3390/vaccines14090776 (registering DOI) - 5 Sep 2026

Abstract

Background/Objectives: Rural populations in the United States experienced consistently lower COVID-19 vaccination rates than urban populations during the pandemic. While barriers to vaccination have been well documented, less is known about facilitators of uptake in rural settings. This study aimed to identify facilitators [...] Read more.

Background/Objectives: Rural populations in the United States experienced consistently lower COVID-19 vaccination rates than urban populations during the pandemic. While barriers to vaccination have been well documented, less is known about facilitators of uptake in rural settings. This study aimed to identify facilitators of COVID-19 vaccination in rural communities from the perspectives of Washington State University (WSU) Extension personnel and to examine these factors using the Consolidated Framework for Implementation Research (CFIR) Outer Setting domain. Methods: A qualitative descriptive study was conducted using semi-structured key informant interviews with WSU Extension personnel. Twenty-one participants representing 34 of 40 Extension offices across Washington State were interviewed in Fall 2023. Interviews were transcribed, de-identified, and analyzed using deductive thematic analysis. Findings were organized into the seven CFIR Outer Setting constructs: critical incidents, local attitudes, local conditions, partnerships and connections, policies and laws, financing, and external pressures. Results: Perceived facilitators of COVID-19 vaccination were identified across all CFIR Outer Setting constructs. Trust emerged as a central theme, with participants reporting that vaccine acceptance was higher when information was delivered by trusted local sources, including Extension personnel, healthcare providers, community leaders, and informal networks. Participants described leveraging partnerships with public health agencies, schools, faith-based organizations, and community groups as enhancing outreach and information dissemination. Additional facilitators identified by participants included no-cost vaccine and personal protective equipment availability, accessible community-based vaccination sites, culturally appropriate educational materials, and coordinated communication systems. Conclusions: Rural vaccination efforts were supported by trust, strong community partnerships, and locally tailored strategies. These findings may inform future public health emergency responses in rural communities. Full article

(This article belongs to the Special Issue SARS-CoV-2, Influenza and Other Respiratory Viruses: Preventive Measures Affecting the Determinants of Health and Disease)

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19 pages, 394 KB

Open AccessReview

Whole-Cell and Acellular Pertussis Vaccines: A Narrative Review of Biological, Clinical, Safety and Programmatic Evidence, with Implications for Poland

by Andrzej Fal, Iwona Paradowska-Stankiewicz, Aneta Nitsch-Osuch and Ernest Kuchar

Vaccines 2026, 14(9), 775; https://doi.org/10.3390/vaccines14090775 - 3 Sep 2026

Abstract

Background/Objectives: Pertussis has resurged worldwide despite long-standing vaccination programs. Whole-cell (wP) and acellular (aP) pertussis vaccines differ in immunobiology, durability, reactogenicity, and programmatic use. Poland is the only European Union/European Economic Area (EU/EEA) country that routinely primes infants with wP while using aP [...] Read more.

Background/Objectives: Pertussis has resurged worldwide despite long-standing vaccination programs. Whole-cell (wP) and acellular (aP) pertussis vaccines differ in immunobiology, durability, reactogenicity, and programmatic use. Poland is the only European Union/European Economic Area (EU/EEA) country that routinely primes infants with wP while using aP products for boosters, pregnancy, and selected indications, providing an informative programmatic context. This review compares both platforms across biological, clinical, safety, epidemiological, and supply domains. Methods: We conducted a narrative review of PubMed/MEDLINE literature and documents from the World Health Organization, European Centre for Disease Prevention and Control, national public health institutes, and regulatory authorities through July 2026. No protocol was registered and no quantitative synthesis was performed. Results: wP priming induces a persistent T-helper 1/T-helper 17-oriented response and an immunoglobulin G1-dominant profile, whereas aP vaccination produces higher, higher-avidity antibody concentrations, an increasing immunoglobulin G4 fraction, and substantially lower reactogenicity. Historical trials demonstrated marked product-level heterogeneity: efficacy ranged from 36–48% for poorly performing wP vaccines to 84–85% for multicomponent aP vaccines, while one United Kingdom wP product performed comparably to a five-component aP vaccine. Protection after aP schedules wanes within several years, no validated correlate of protection exists, and neither intramuscular platform reliably prevents colonization or transmission. In 2024, eight aP-using EU/EEA countries had higher pertussis notification rates than Poland despite stable Polish infant coverage. Conclusions: Neither platform is uniformly superior across products, schedules, and clinically relevant outcomes. Program performance depends primarily on timely infant vaccination, maternal vaccination, appropriate boosters, product-specific effectiveness evidence, and secure vaccine supply. Full article

(This article belongs to the Special Issue The Role of Vaccination on Public Health and Epidemiology)

30 pages, 4742 KB

Open AccessArticle

A Chimeric Virus Approach Reveals the Matrix (M) Gene as a Critical Modulator of Mumps Virus Neurovirulence

by Christian J. Sauder, Malen Link, Laurie Ngo, Cheryl Zhang, Chao-Kai Chou, Wells W. Wu, Tatiana Zagorodnyaya, Majid Laassri and Steven Rubin

Vaccines 2026, 14(9), 774; https://doi.org/10.3390/vaccines14090774 - 3 Sep 2026

Abstract

Background/Objectives: Live attenuated mumps virus (MuV) vaccine strains have significantly reduced disease incidence since their introduction in the 1960s; however, a recent resurgence of outbreaks has led to calls for the development of new vaccines to overcome what appears to be reduced [...] Read more.

Background/Objectives: Live attenuated mumps virus (MuV) vaccine strains have significantly reduced disease incidence since their introduction in the 1960s; however, a recent resurgence of outbreaks has led to calls for the development of new vaccines to overcome what appears to be reduced effectiveness linked to waning immunity and the emergence of strains antigenically mismatched to vaccine strains. A major obstacle to the development of newer live, attenuated MuV vaccines is ensuring their safety, particularly given the virus’s neurotropic properties. Indeed, several vaccine strains licensed for use outside the US have proven to be insufficiently attenuated (such as the Urabe AM9 vaccine strain) and have caused aseptic meningitis in recipients, despite efforts to test these strains for neurotoxicity pre-licensure. Historically, attenuation was achieved empirically, and pre-clinical testing for neurovirulence safety has proven unreliable. Despite efforts in recent years, the genetic basis of attenuation of MuV vaccines remains inadequately understood. The objective of this study was to elucidate the genetic basis of neurovirulence of the Urabe AM9 vaccine strain. Methods: To this end, we generated a series of chimeric viruses in which genes of the highly attenuated Jeryl Lynn (JL) vaccine strain were exchanged with corresponding genes from the Urabe AM9 vaccine strain. The resulting chimeric viruses were tested for neurovirulence in a rat model and characterized for replication in vitro and in vivo. Using a multi-tiered approach consisting of independent rescue and analysis of two to three viruses per cDNA construct, possible off-target effects of identified single-nucleotide heterogeneities were mitigated. Results: All viruses were shown to be replication-competent in Vero cells, but differences in replication efficiencies and virus-induced neurotoxicity were observed in the in vivo model. In a rat neuronal cell line, the Urabe AM9 M and HN genes had opposite effects on the growth of chimeric JL- and Urabe AM9-based viruses. Conclusions: The results presented herein indicate that MuV neuroattenuation is mediated by the concerted action of multiple genes, with the matrix (M) gene exerting a dominant effect. These findings contribute to a growing body of evidence that informs the rational design of next-generation live-attenuated mumps virus vaccines. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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14 pages, 3023 KB

Open AccessArticle

A Randomized Phase 3 Study to Evaluate the Safety, Tolerability, and Immunogenicity of the Bivalent RSVpreF Vaccine in Older Adults in Korea

by Won Suk Choi, Karen Quan, James A. Baber, Anna Jaques, Karla Janse van Rensburg, Wen Li, Mark W. Cutler, Elena V. Kalinina, Annaliesa S. Anderson, Kena A. Swanson, Alejandra Gurtman and Iona Munjal

Vaccines 2026, 14(9), 773; https://doi.org/10.3390/vaccines14090773 - 3 Sep 2026

Abstract

Background/Objectives: The bivalent RSVpreF vaccine is effective at preventing respiratory syncytial virus (RSV)-associated lower respiratory tract illness in adults. However, data regarding safety and immunogenicity of RSVpreF in Korean populations are limited. Methods: This was a phase 3, multicenter, placebo-controlled, randomized [...] Read more.

Background/Objectives: The bivalent RSVpreF vaccine is effective at preventing respiratory syncytial virus (RSV)-associated lower respiratory tract illness in adults. However, data regarding safety and immunogenicity of RSVpreF in Korean populations are limited. Methods: This was a phase 3, multicenter, placebo-controlled, randomized (2:1), double-blind study in Korean adults 60 years of age and older. Participants received a single 120-μg dose of RSVpreF or matching placebo. Safety endpoints included local reactions and systemic events through 7 days and adverse events (AEs) through 1 month after vaccination, and serious AEs (SAEs) throughout the study. RSV-A and RSV-B serum 50% neutralizing geometric mean titers (GMTs) and geometric mean fold rises (GMFRs) were obtained 1 month after vaccination. Results: Overall, 377 participants received study intervention (RSVpreF, n = 251; placebo, n = 126). Most local reactions and all systemic events were of mild or moderate severity. Injection-site pain was the most frequently reported local reaction (RSVpreF, 12.4%; placebo, 3.2%). The most frequently reported systemic events were fatigue (RSVpreF, 23.1%; placebo, 26.2%) and muscle pain (RSVpreF, 15.5%; placebo, 9.5%). AEs through 1 month after vaccination were infrequent (RSVpreF, 3.6%; placebo, 0.8%); none were considered vaccine related by the investigator. RSV-A and RSV-B neutralizing GMTs increased 1 month after RSVpreF, with GMFRs (95% CIs) from before to 1 month after vaccination of 9.5 (8.51–10.67) for RSV-A and 8.3 (7.37–9.39) for RSV-B. Conclusions: In older Korean adults, RSVpreF had an acceptable safety and tolerability profile and elicited robust RSV neutralizing responses 1 month after vaccination consistent with pivotal phase 3 efficacy trial results. ClincalTrials.gov Identifier: NCT06593587 (date of registration: 9 September 2024). Full article

(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)

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13 pages, 594 KB

Open AccessReview

An Analysis of Multilevel Barriers to Human Papillomavirus Vaccination Uptake Among Rural U.S. Adolescents

by Tajauna Batchelor, Madison Brown, Kimbrionna Hunter, Asma Hanif and Shumaila Nida Javed Tunio

Vaccines 2026, 14(9), 772; https://doi.org/10.3390/vaccines14090772 - 2 Sep 2026

Abstract

Despite longstanding vaccine availability, human papillomavirus (HPV) remains the most common sexually transmitted infection in the United States and a leading cause of preventable cancers. Additionally, HPV vaccination rates remain below other routinely recommended adolescent immunizations, particularly in rural populations. This study aimed [...] Read more.

Despite longstanding vaccine availability, human papillomavirus (HPV) remains the most common sexually transmitted infection in the United States and a leading cause of preventable cancers. Additionally, HPV vaccination rates remain below other routinely recommended adolescent immunizations, particularly in rural populations. This study aimed to identify barriers related to healthcare access, socioeconomic conditions, cultural beliefs, and provider–patient communication in rural communities. A bibliographical review of articles published in English from 2020 to 2025 and an analysis of national datasets were conducted to establish trends in HPV vaccination rates. State-level HPV vaccination data for adolescents aged 13–17 years were obtained from America’s Health Rankings and the Centers for Disease Control and Prevention National Immunization Survey-Teen. States were classified as predominantly rural or urban using Rural–Urban Continuum Codes, and mean vaccination completion rates were compared. The mean HPV vaccination completion rate was lower in rural states (60.55%) compared to urban states (67.31%); however, this difference did not meet the selected threshold for statistical significance (p = 0.025). Barriers identified in the literature included reduced access to healthcare, differences in provider communication, socioeconomic constraints, and limited health literacy in rural communities. Of the identified barriers, healthcare provider recommendations emerged as one of the strongest predictors of vaccine acceptance. These findings highlight multilevel determinants contributing to differences in HPV vaccine uptake and underscore the need for targeted, evidence-based strategies to improve vaccine access and coverage in underserved adolescent populations. Full article

(This article belongs to the Special Issue Prevention of Human Papillomavirus (HPV) and Vaccination)

16 pages, 3674 KB

Open AccessArticle

Metabolic Signatures Associated with COVID-19 Vaccination in Serum from Healthy Individuals

by Mariam M. AlEissa, Refat M. Nimer, Reem H. AlMalki, Randh AlAhmari, Ahdab A. Alsaieedi, Monera Alrukhayes, Nada Saleh, Raef R. Albugami, Raghad A. AlQurashi, Esraa A. Hawsa, Muath Ben Shaded, Afshan Masood, Sami S. Almudarra, Assim A. Alfadda, Hamad H. Alonazi, Abdullah M. Assiri and Anas Abdel Rahman

Vaccines 2026, 14(9), 771; https://doi.org/10.3390/vaccines14090771 - 2 Sep 2026

Abstract

Background: COVID-19 vaccines have proven effective in reducing severe disease and mortality from SARS CoV-2 infection. The underlying molecular mechanisms and alterations in the human serum metabolome influencing the effectiveness and development of immunity remain unclear. Methods: Serum samples were collected from [...] Read more.

Background: COVID-19 vaccines have proven effective in reducing severe disease and mortality from SARS CoV-2 infection. The underlying molecular mechanisms and alterations in the human serum metabolome influencing the effectiveness and development of immunity remain unclear. Methods: Serum samples were collected from 29 healthy individuals at three time points: prior to vaccination (A), post-first dose (B), and post-second dose (C). Untargeted high-resolution (HR) liquid chromatography coupled with mass spectrometry (LC-MS) was performed on these samples. Metabolites showing significant differential abundance at each time point were identified, and both multivariate and univariate statistical analyses were performed to determine changes associated with the pairwise comparisons, priming (A vs. B), booster (B vs. C), and the overall vaccine effect (A vs. C). Vaccination-specific features were determined after excluding metabolites associated with SARS-CoV-2 IgG seropositivity to better isolate vaccine-driven metabolic changes. Bioinformatics, pathway, and network analyses were conducted using Ingenuity Pathway Analysis (IPA) to identify relevant pathways. Results: Our study identified significant metabolic changes across the three time points. A total of 377 metabolites were identified, of which 59 metabolites, including prostaglandins, eicosanoids, and lipids, were shared across all three groups. The majority of these metabolites showed an initial decrease after the first dose, followed by broad upregulation after the second dose. We identified 1 (downregulated), 34 (26 upregulated and 8 downregulated), and 18 (2 upregulated and 16 downregulated) unique metabolites in the priming, booster, and the overall vaccine effect groups, respectively. L-3-hydroxykynurenine was observed to be significantly reduced by the priming dose effect. By contrast, the booster effect showed decreased myo-inositol 1,3,4,5-tetrakisphosphate, while levels of DL-DOPA, 3-methoxytyrosine, and prostaglandin-esterified phospholipids, including PC(P-16:0/PGF1α) and PE(PGF1α/18:0), increased. On the other hand, the overall vaccine effect revealed decreased cyclic AMP and increased 3′-O-methyladenosine levels. These changes were associated with perturbations in arachidonic acid metabolism, glycerophospholipid metabolism, arginine biosynthesis, and steroid hormone biosynthesis. IPA network analysis identified AKT, TP53, EGFR, and cAMP as key dysregulated nodes. Conclusions: Longitudinal metabolomic profiling demonstrated that COVID-19 vaccination induced distinct but interrelated biochemical changes throughout the vaccination course. The priming dose induced a limited set of early metabolic changes, whereas the booster was associated with more significantly changed metabolites that were involved in lipid, bile acid, steroid, amino acid, and nucleotide pathways. Together, these findings indicate that sequential vaccination is associated with dose-dependent systemic metabolic adaptation, with the booster dose having the largest number of dysregulated metabolites. Full article

(This article belongs to the Special Issue COVID-19 Vaccination and Public Health: Addressing Global, Regional and Within-Country Inequalities)

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21 pages, 3574 KB

Open AccessArticle

How Does Inter-Epitope Spacer Variation Within Artificial Immunogens Based on T-Cell Epitopes of Tick-Borne Encephalitis Virus Affect Immunogenicity?

by Elena V. Yakovleva, Denis V. Antonets, Mariya B. Borgoyakova, Ekaterina V. Starostina, Vladimir A. Yakovlev, Elizaveta V. Shaburova, Denis N. Kisakov, Lyubov A. Kisakova, Olga Y. Volkova, Nadezhda B. Rudometova, Andrey P. Rudometov and Larisa I. Karpenko

Vaccines 2026, 14(9), 770; https://doi.org/10.3390/vaccines14090770 - 2 Sep 2026

Abstract

Background/Objectives: In recent years, researchers have directed considerable attention toward the activation of the T-cell response in the development of vaccines against viral infections, including the tick-borne encephalitis virus (TBEV). A particularly promising approach to developing effective and safe T-cell vaccines involves the [...] Read more.

Background/Objectives: In recent years, researchers have directed considerable attention toward the activation of the T-cell response in the development of vaccines against viral infections, including the tick-borne encephalitis virus (TBEV). A particularly promising approach to developing effective and safe T-cell vaccines involves the use of artificial multi-epitope immunogens. The selection of spacers that link epitopes within a construct can have a significant effect on the immunogenicity of multi-epitope constructs. The objective of this study was to design multi-epitope TBEV immunogens using various spacers and to evaluate their immunogenicity. Methods: The present study involved the design of three multi-epitope immunogens, which were developed based on T-cell epitopes from TBEV proteins. The AG1-ub construct contained optimized alanine spacers, the AG2-ub construct contained GPGPG spacers, and the AG4-ub construct contained no spacers. Three DNA vaccines encoding the designed immunogens were subsequently produced. To assess the immunogenicity of the constructs, BALB/c mice were immunized with the designed DNA vaccines via electroporation. Results: The ELISpot assay demonstrated that DNA vaccines encoding AG1-ub and AG4-ub induced a significant number of IFN-γ-producing cells. The DNA vaccine encoding AG2-ub, a multi-epitope with GPGPG spacers, exhibited low immunogenicity, potentially attributable to inadequate processing or misfolding of the AG2-ub protein, thereby affecting the molecule’s structure. Conclusions: The data provided in this study on the effect of spacers on the immunogenicity of multi-epitope constructs can be used to optimize the design of vaccine candidates. However, further research is needed to assess their clinical potential. Full article

(This article belongs to the Section Vaccine Design, Development, and Delivery)

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16 pages, 2147 KB

Open AccessArticle

Immunization with mRNA-LNP Elicits De Novo IgG Responses in the Presence of Maternal Antibody

by John M. Ramos, Brittany Plummer, Christian R. Binuya, Mackensie Gross, Adelaide S. Fuller, Krithika P. Karthigeyan, Savannah Berrios, Sallie R. Permar and Caitlin A. Williams

Vaccines 2026, 14(9), 769; https://doi.org/10.3390/vaccines14090769 - 2 Sep 2026

Abstract

Background/Objectives: Maternal antibodies can inhibit vaccine-specific humoral responses in early life, leaving infants at increased risk for severe disease for vaccine-preventable infections. In the case of SARS-CoV-2, infants under the age of 3 months represented most child hospitalizations, yet there is no approved [...] Read more.

Background/Objectives: Maternal antibodies can inhibit vaccine-specific humoral responses in early life, leaving infants at increased risk for severe disease for vaccine-preventable infections. In the case of SARS-CoV-2, infants under the age of 3 months represented most child hospitalizations, yet there is no approved vaccine for children under the age of 6 months. There is a clear need for effective immunization in early life to prevent infant morbidity and mortality. Here, we established a mouse model to define how maternally derived antibodies shape early-life responses to mRNA vaccination. Methods: Adult female mice were immunized with PBS or 5 mcg of the SARS-CoV-2 mRNA-1273 vaccine via intramuscular injection and paired with a male. Pups from subsequent litters were immunized with PBS or 5 mcg of mRNA-1273 vaccine via intramuscular injection. Peripheral blood and spleens were collected at time points post-immunization. We measured vaccine-elicited anti-Spike IgG in mouse pups exposed or unexposed to vaccine-specific maternal IgG. Results: Spike-specific maternal IgG is detectable at high levels immediately after pup immunization or mock immunization; however, in mock immunized pups, it wanes by three weeks post-pup immunization. Pups born to immunized dams developed Spike specific IgG comparable to pups born to naïve dams. IgG subclass analyses distinguished passively acquired antibodies from vaccine-induced responses. Despite robust binding antibody responses, neutralizing activity against D614G pseudovirus was heterogeneous and did not scale proportionally with IgG titers, showing qualitative differences in early-life humoral immunity. Splenic Spike-specific B cell frequencies and T follicular helper (Tfh) cell responses were detectable in vaccinated pups irrespective of maternal immunization status, with Tfh cell frequencies peaking at day 7 post-immunization in both groups. Conclusions: Using SARS-CoV-2 as a model pathogen, we found that early-life mRNA vaccination can elicit humoral immune responses in the presence of maternal antibodies. Furthermore, the presence of maternal antibody did not inhibit the development of antigen-specific B cells or Tfh cells in the spleen. Our findings support the potential of extending vaccination strategies into early infancy and provide a framework for optimizing mRNA-based vaccine timing and design in the context of maternal immunity. Full article

(This article belongs to the Special Issue Innovations in Vaccines for Poorly Responding Populations)

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29 pages, 489 KB

Open AccessReview

Maternal Immunization Against Respiratory Syncytial Virus: An Updated WAidid Consensus Document on Evidence, Implementation, and Public Health Priorities

by Susanna Esposito, Matteo Riccò, Bahaa Abu-Raya, Giancarlo Icardi, Vana Spoulou, David Greenberg, Oana Falup Pecurariu, Ivan Fan-Ngai Hung, Albert Osterhaus, Vittorio Sambri and Nicola Principi

Vaccines 2026, 14(9), 768; https://doi.org/10.3390/vaccines14090768 - 2 Sep 2026

Abstract

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease and hospitalization in early infancy. The availability of maternal RSVpreF vaccination and long-acting infant monoclonal antibodies has created two effective but operationally distinct pathways for passive protection. Methods: This [...] Read more.

Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease and hospitalization in early infancy. The availability of maternal RSVpreF vaccination and long-acting infant monoclonal antibodies has created two effective but operationally distinct pathways for passive protection. Methods: This WAidid consensus document focuses on maternal RSV immunization within an integrated early infancy prevention strategy. A multidisciplinary Consensus Development Group reviewed evidence on infant RSV burden and seasonality, maternal vaccine efficacy and effectiveness, transplacental antibody transfer, long-acting monoclonal antibodies, implementation, equity, and economic considerations. Recommendations were developed using a modified Delphi process with a prespecified consensus threshold of at least 75% agreement. Results: Maternal vaccination can provide protection from birth when administered sufficiently before delivery, whereas direct infant monoclonal antibody prophylaxis provides rapid protection independent of maternal immune response and placental transfer. The relative value of the two approaches depends on gestational age, vaccination-to-delivery interval, infant risk, birth timing, local RSV circulation, antenatal care access, product availability, and cost. Post-pandemic disruption of RSV seasonality increases the importance of flexible strategies that protect infants born outside historically defined seasonal windows. Direct head-to-head evidence remains limited; therefore, policy decisions should integrate trial efficacy, emerging real-world effectiveness, implementation feasibility, and local epidemiology rather than assume universal superiority of one strategy. Conclusions: Maternal vaccination and infant monoclonal antibodies should be positioned within a coordinated prevention pathway. Maternal vaccination may serve as the principal strategy for appropriately timed pregnancies with reliable antenatal access, while infant monoclonal antibodies are particularly important when maternal vaccination is absent, too close to delivery, or potentially ineffective, or when the infant is preterm or otherwise at increased risk. Surveillance and locally adapted implementation are essential to maintain protection as RSV epidemiology evolves. Full article

(This article belongs to the Special Issue Recent Progress of Vaccines for Respiratory Syncytial Virus (RSV))

15 pages, 527 KB

Open AccessArticle

High Hepatitis A Virus Seroprevalence and Low Self-Reported Vaccination Coverage Among Waste Collection Workers in Sardinia, Italy: A Retrospective Cross-Sectional Study

by Sara Maria Pani, Luigi Isaia Lecca, Sergio Pili, Ilaria Pilia, Vitalba Milazzo and Marcello Campagna

Vaccines 2026, 14(9), 767; https://doi.org/10.3390/vaccines14090767 - 2 Sep 2026

Abstract

Background/Objectives: Hepatitis A virus (HAV) infection is a relevant biological risk in some occupational settings and has long been discussed as an occupational health concern among municipal waste collection workers. Data on HAV seroprevalence and vaccination history in this occupational group remain limited [...] Read more.

Background/Objectives: Hepatitis A virus (HAV) infection is a relevant biological risk in some occupational settings and has long been discussed as an occupational health concern among municipal waste collection workers. Data on HAV seroprevalence and vaccination history in this occupational group remain limited in Italy. This study investigated HAV seroprevalence, self-reported vaccination history, and factors associated with HAV seropositivity among waste collection workers in Sardinia. Methods: This retrospective cross-sectional study analyzed HAV seroprevalence and self-reported vaccination history among 326 workers in Sardinia, Italy, using occupational health surveillance data (2017–2024). Recorded variables included age, sex, smoking habits, years of service, work setting, vaccination status, and serological results. Chi-square and Mann–Whitney U tests assessed group differences; logistic regression identified factors independently associated with HAV seropositivity. Results: HAV seroprevalence was 44.2%; only 0.9% of participants reported previous HAV vaccination. Multivariable analysis identified older age, but not years of service, as independently associated with HAV seropositivity once age was modeled as a continuous variable—a pattern more consistent with birth-cohort differences in lifetime HAV exposure than with cumulative occupational exposure. Worksite 7 showed a higher prevalence ratio of HAV seropositivity relative to the reference site, but this finding was based on a small subsample and should be considered exploratory; observed worksite-level differences may reflect organizational rather than geographic factors. Conclusions: Older age, rather than occupational tenure, was independently associated with HAV seropositivity among Sardinian waste workers, a pattern consistent with birth-cohort differences in lifetime exposure. The high seroprevalence and very low vaccination uptake highlight the need to strengthen prevention through improved vaccination access, awareness, and better integration of occupational and public health strategies. Full article

(This article belongs to the Special Issue Vaccination Against Viral Hepatitis for Prevention and Treatment)

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18 pages, 3336 KB

Open AccessArticle

The African Polio Laboratory Network: Advancing Regional Poliovirus Detection, Genomic Surveillance, and Eradication

by Brook Tesfaye, Terna Nomhwange, Shelina Moonsamy, Julius E. Chia, Maryceline M. Baba, Adedayo Omotayo Fanaye, Mesfin Tefera, Yogolelo Riziki, Peter Borus, Josephine Bwogi, Marie-Claire Endegue, Mariette Glitho, Idah Ndumba, Priscilla Mosoke, Ousmane M. Diop, John Kofi Odoom, Martin Faye, Gedi Mohamed and Anfumbom Kfutwah

Vaccines 2026, 14(9), 766; https://doi.org/10.3390/vaccines14090766 - 2 Sep 2026

Abstract

Background: Sustaining progress toward polio eradication requires not only effective vaccination but also a resilient laboratory network capable of timely poliovirus detection, confirmation, and genetic characterization. In the WHO African region, the African polio laboratory network provides essential virological support for eradication efforts; [...] Read more.

Background: Sustaining progress toward polio eradication requires not only effective vaccination but also a resilient laboratory network capable of timely poliovirus detection, confirmation, and genetic characterization. In the WHO African region, the African polio laboratory network provides essential virological support for eradication efforts; however, persistent circulating Vaccine-derived Polioviruses (cVDPVs) outbreaks and increasing demands of genomic surveillance continue to challenge laboratory capacity. Despite its critical role, evidence describing the operational performance, adaptive capacity, and evolution of regional polio laboratory network remains limited. This study evaluates the performance and operational experience of the African polio laboratory network in 2025, highlighting contributions to poliovirus detection, genomic surveillance, quality assurance, and outbreak response, while sharing lessons to inform regional public health systems. Methods: A retrospective secondary data analysis was conducted using laboratory surveillance and outbreak databases, supplemented by reviews of programmatic reports. Data were cleaned and harmonized prior to analysis. Descriptive analyses were performed to assess laboratory workload, timeliness indicators, genomic capacity, quality assurance performance, and operational challenges. Qualitative review of programmatic documents was conducted to identify contextual factors influencing performance. Results: In 2025, 77,230 Acute Flaccid Paralysis (AFP) specimens were analyzed across 16 laboratories. Ninety-two percent of specimens met the timeliness target for virus isolation, and 94% met the target for PCR-ITD. Genomic sequencing confirmed 20 cVDPV outbreaks in 10 countries. The establishment of new sequencing laboratories in Uganda and Nigeria reduced turnaround times, and a 2025 expansion plan aimed to build sequencing capacity in 12 additional countries. All laboratories assessed in 2024 for virus isolation, PCR-ITD, and environmental surveillance exceeded quality assurance accreditation thresholds and were rated “Pass”. The pilot implementation of Direct Detection Nanopore Sequencing (DDNS) techniques is expected to further strengthen genomic surveillance. Challenges remain, including stock out of essential supplies, uneven workloads, and infrastructure gaps. Conclusions: The African polio laboratory network has demonstrated sustained capacity, adaptability, and innovation in supporting polio eradication activities in the WHO African region. This study provides evidence on the importance of strengthening laboratory systems, expanding genomic capacity, and maintaining quality assurance mechanisms to support the final phase of polio eradication and broader public health surveillance. Full article

(This article belongs to the Section Vaccines and Public Health)

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24 pages, 719 KB

Open AccessArticle

Seroepidemiological Characteristics and Influencing Factors of Hepatitis B Virus Infection Among Pregnant Women in Nanning City, China (2024–2025): A Cross-Sectional Study

by Chang Huang, Tao Lan, Bin Xu, Qiuyun Deng and Chi Tang

Vaccines 2026, 14(9), 765; https://doi.org/10.3390/vaccines14090765 - 1 Sep 2026

Abstract

Objectives: This cross-sectional study characterized HBV serological profiles and associated factors among pregnant women in Nanning to inform targeted MTCT prevention strategies. Methods: A total of 1935 pregnant women were enrolled via stratified cluster random sampling from October 2024 to May 2025. Five [...] Read more.

Objectives: This cross-sectional study characterized HBV serological profiles and associated factors among pregnant women in Nanning to inform targeted MTCT prevention strategies. Methods: A total of 1935 pregnant women were enrolled via stratified cluster random sampling from October 2024 to May 2025. Five HBV serological markers were quantified by chemiluminescence immunoassay. Multivariable analysis identified factors associated with HBsAg, HBsAb, and HBcAb positivity. HBsAb geometric mean concentration (GMC) and ratio (GMR) were calculated. Results: The overall seropositivity rates (with 95% CI) of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb were 6.98% (5.92–8.20%), 59.48% (57.28–61.65%), 1.50% (1.05–2.14%), 15.50% (13.96–17.18%), and 33.02% (30.96–35.15%), respectively. HBsAg, HBeAb, and HBcAb positivity increased with age. The HBsAb GMC among uninfected pregnant women was 4.63 mIU/mL (95% CI: 3.72–5.75). Rural pregnant women had lower HBsAb seropositivity than urban counterparts. Unvaccinated women or those with unknown vaccination status showed higher HBsAg, HBeAg, HBeAb, and HBcAb positivity, and lower HBsAb seropositivity, compared with vaccinated women. Advanced age, chronic comorbidities, and HBV exposure were risk factors for HBsAg positivity, whereas HBV vaccination was protective. For HBsAb, higher education and vaccination were protective; advanced age, rural residence, chronic comorbidities, and non-medical occupations were risk factors. For HBcAb, advanced age, chronic comorbidities, and HBV exposure were risk factors, while higher education and vaccination were protective. Conclusions: Pregnant women in Nanning have a high HBV prevalence and insufficient immune protection. Targeted prevention strategies for reproductive-age women are urgently needed to reduce vertical transmission risk. Full article

(This article belongs to the Special Issue Vaccination Against Viral Hepatitis for Prevention and Treatment)

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18 pages, 710 KB

Open AccessSystematic Review

Knowledge, Attitudes, and Perceptions of HPV Vaccination for Adolescents with Intellectual Disabilities: A Systematic Review

by Giuseppina Lo Moro, Erica De Vita and Gianluca Voglino

Vaccines 2026, 14(9), 764; https://doi.org/10.3390/vaccines14090764 - 1 Sep 2026

Abstract

Background/Objectives: Adolescents with intellectual disabilities may experience inequities in preventive healthcare, including HPV vaccination. This review aimed to synthesize evidence on HPV vaccination-related knowledge, attitudes and perceptions among adolescents with intellectual disabilities, parents/caregivers, educators, healthcare professionals and other stakeholders. Methods: A systematic search [...] Read more.

Background/Objectives: Adolescents with intellectual disabilities may experience inequities in preventive healthcare, including HPV vaccination. This review aimed to synthesize evidence on HPV vaccination-related knowledge, attitudes and perceptions among adolescents with intellectual disabilities, parents/caregivers, educators, healthcare professionals and other stakeholders. Methods: A systematic search was conducted in PubMed, Embase and Scopus on 29 October 2025. Eligible studies reported original data on knowledge, attitudes or perceptions regarding HPV vaccination for adolescents with intellectual disabilities or relevant stakeholders. The protocol was registered on PROSPERO (CRD420251015183). Quantitative, qualitative and mixed-methods studies were considered. Results: Seven studies were included. They were conducted in the USA, Australia and the UK and involved parents/caregivers, healthcare providers, school staff, immunization staff and adolescents or young people with disabilities. Direct evidence from adolescents was limited. HPV-related knowledge was often limited or uneven, and standard information materials were perceived as insufficiently accessible. Parents/caregivers were often broadly supportive of vaccination, but HPV-specific acceptance was affected by perceived low susceptibility, assumptions about sexual inactivity, safety concerns, procedure-related distress and lack of provider recommendation. Healthcare providers generally supported HPV vaccination; however, recommendations were sometimes influenced by perceived sexual activity, age or consent. School-based vaccination was considered useful but required tailored information, preparation, individual adjustments and follow-up. Conclusions: Evidence on HPV vaccination-related knowledge, attitudes and perceptions among adolescents with intellectual disabilities and their stakeholders remains limited and geographically restricted. Improving equitable access may require interventions that should be further investigated, such as accessible communication, systematic provider recommendation, flexible vaccination pathways and greater involvement of adolescents in decision-making. Full article

(This article belongs to the Special Issue Advancing Public Health Through Vaccination: 2nd Edition)

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15 pages, 240 KB

Open AccessArticle

Factors Associated with Intention to Be Vaccinated Against Seasonal Influenza in Healthcare Workers: A Cross-Sectional Study Assessing Health Belief Model Constructs in Serbia

by Larisa Vujnovic, Biljana Kilibarda, Sofija Jovanovic, Dragana Dimitrijevic, Milunka Milinkovic, Zoran Bukumiric and Verica Jovanovic

Vaccines 2026, 14(9), 763; https://doi.org/10.3390/vaccines14090763 - 1 Sep 2026

Abstract

Introduction: As seasonal influenza vaccination coverage among healthcare workers (HCWs) in Serbia remains suboptimal, we aimed to identify HCW beliefs associated with their intention to receive seasonal influenza vaccine (“vaccination intention”) in the season 2024/2025. Methods: In a cross-sectional survey conducted in 2024, [...] Read more.

Introduction: As seasonal influenza vaccination coverage among healthcare workers (HCWs) in Serbia remains suboptimal, we aimed to identify HCW beliefs associated with their intention to receive seasonal influenza vaccine (“vaccination intention”) in the season 2024/2025. Methods: In a cross-sectional survey conducted in 2024, healthcare institutions were selected from a national registry, using multi-stage sampling stratified by geographical region and healthcare level. All consenting HCWs present on the survey day self-completed questionnaires. Five dichotomised Health Belief Model constructs were assessed: perceived susceptibility to influenza, perceived disease severity, perceived vaccination benefits, perceived physical and psychological barriers, and perceived cues for action (recommendation by another HCW, someone close, or a supervisor). The association of vaccination intention (yes/no/undecided) with Health Belief Model constructs, demographic and occupational factors were assessed using multinomial logistic regression. Results: Of 1919 respondents, 30% declared positive vaccination intention, 52.5% no intention, and 17.5% were undecided. Compared with no intention, positive vaccination intention was associated with perceived self-benefit (aOR = 6.22, CI = 3.49–11.08), perceived patient benefit (aOR = 2.26, CI = 1.48–3.45), perceived susceptibility (aOR = 3.26, CI = 2.19–4.86), and perceived vaccine safety (aOR = 2.95, CI = 1.93–4.50). Participants were more likely to be undecided than reject vaccination if they experienced higher perceived susceptibility (aOR = 2.93, CI = 1.89–4.54), perceived influenza as severe (aOR = 2.04, CI = 1.30–3.21), perceived patient benefits (aOR = 1.77, CI = 1.14–2.74), or recalled receiving a recommendation from another HCW (aOR = 2.63, CI = 1.17–5.85). Conclusions: HCWs’ positive vaccination intention was associated with beliefs relevant for personal health and patient benefits. The undecided group showed a distinct pattern of beliefs warranting their separate analysis and specific approaches. Full article

(This article belongs to the Special Issue Factors Affecting Influenza Vaccine Uptake)

13 pages, 1754 KB

Open AccessArticle

Real-World Effectiveness of Egg-Based Inactivated Influenza Vaccines Against Influenza Among Children Aged 6–59 Months During the 2025/26 Season in Shenzhen Area, China: A Retrospective Cohort Study

by Hui-Ling Tan, Wu Li, Yu Zeng, Rui-Kun Zeng, Jia-Xin Zhong and Hou-Ming Wei

Vaccines 2026, 14(9), 762; https://doi.org/10.3390/vaccines14090762 - 31 Aug 2026

Abstract

Background: Young children are at high risk of influenza and its complications, yet evidence on the real-world effectiveness of egg-based inactivated influenza vaccines in children aged 6–59 months remains limited during antigenically drifted seasons. Methods: We conducted a population-based retrospective cohort study using [...] Read more.

Background: Young children are at high risk of influenza and its complications, yet evidence on the real-world effectiveness of egg-based inactivated influenza vaccines in children aged 6–59 months remains limited during antigenically drifted seasons. Methods: We conducted a population-based retrospective cohort study using linked immunization and influenza surveillance records from August 4, 2025 to February 8, 2026. Vaccinated and unvaccinated children aged 6–59 months were matched 1:1 using propensity scores based on demographic characteristics, routine and non-routine vaccination history, prior seasonal influenza vaccination (SIV), and prior influenza infection. For vaccinated children, the index date was defined as the date of the last SIV received during the study period; matched unvaccinated children were assigned the corresponding index date. Follow-up began 14 days later and continued until influenza onset or February 8, 2026. Adjusted vaccine effectiveness (aVE) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Sensitivity analyses included a negative control outcome analysis using varicella infection, a multivariable logistic regression analysis with influenza infection as the outcome, and a time-dependent exposure Cox regression analysis in the full eligible cohort. Results: A total of 26,444 children were included in the final cohort (13,239 vaccinated and 13,205 unvaccinated). Influenza incidence rates were 28.70 and 40.21 per 100 person-years in vaccinated and unvaccinated groups, respectively. The aVE was 28.82% (95% CI: 23.07–34.14%). aVE was generally consistent across most subgroups, but was lower in children vaccinated in the previous season than in those without prior-season vaccination (20.41% vs. 34.28%; p for interaction = 0.016). Sensitivity analyses yielded comparable VE estimates. Conclusions: Egg-based inactivated influenza vaccination conferred moderate real-world protection against influenza in children aged 6–59 months during the 2025/26 season. Continued monitoring of vaccine effectiveness is needed to inform vaccination strategies in young children. Full article

(This article belongs to the Special Issue The Effectiveness of Influenza Vaccine)

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33 pages, 975 KB

Open AccessArticle

Development and Initial Validation of a Multidimensional Instrument for Assessing Determinants of HPV Vaccine Readiness and Uptake Among Caregivers in Pakistan: A PLS-SEM Approach

by Khola Noreen, Samina Naeem Khalid, Saba Maryam, Mehreen Noor and Abdul Momin Rizwan Ahmad

Vaccines 2026, 14(9), 761; https://doi.org/10.3390/vaccines14090761 - 31 Aug 2026

Abstract

Background: HPV vaccination coverage in Pakistan is extremely low, and there are complex psychosocial, cultural, and logistical barriers that currently impede vaccinations. There is no validated measurement tool that is appropriate to the context to measure these determinants systematically. Objective: To [...] Read more.

Background: HPV vaccination coverage in Pakistan is extremely low, and there are complex psychosocial, cultural, and logistical barriers that currently impede vaccinations. There is no validated measurement tool that is appropriate to the context to measure these determinants systematically. Objective: To develop and validate a multidimensional instrument measuring important factors associated with HPV vaccine uptake and readiness in Pakistan through partial least squares structural equation modelling (PLS-SEM). Methods: A cross-sectional survey was administered to caregivers of girls aged 9–16 years, recruited via purposive/convenience sampling from schools, EPI sites, and household outreach in three Punjab/ICT districts (Rawalpindi, Islamabad, Bahawalpur) during September–November 2025, coinciding with Pakistan’s national HPV vaccination campaign (700 initial responses; 639 retained after screening). The instrument comprised 75 initial items across six constructs: thinking and feeling, social processes, motivation, practical issues, cultural integration, and the vaccination uptake composite index (a composite index of actual vaccination receipt, intention, perceived importance, and perceived access). The measurement model was evaluated for indicator/construct reliability, convergent validity (AVE), and discriminant validity (HTMT, Fornell–Larcker, cross-loadings); the structural model tested direct effects, mediation via motivation, and moderation by practical issues and cultural integration. Results: The number of indicators after model refinement was 27 in six constructs. All outer loadings exceeded 0.70 (range: 0.765–0.939). Cronbach’s α ranged from 0.854 to 0.928, composite reliability from 0.912 to 0.945, and AVE from 0.710 to 0.850. All the HTMT ratios were less than 0.90; Fornell–Larcker and cross-loadings criteria supported discriminant validity. The relationships between thinking and feeling (β = 0.098, p < 0.001) and social processes (β = 0.155, p < 0.001) with vaccination uptake were significantly mediated by motivation. Social and cognitive pathways were moderated by cultural integration. The model accounted for 65.8% of the variance in motivation and 59.4% in uptake of vaccination. Conclusions: The instrument was found to have good psychometric properties and to be suitable suitable for evaluating the determinants of HPV vaccination in conservative, resource-constrained countries such as Pakistan. Findings have direct implications for targeted public health interventions to improve HPV vaccine readiness and uptake. Full article

(This article belongs to the Special Issue Strategies to Increase the Uptake and Delivery of HPV Vaccination in LMICs)

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