Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128149
Zachary H. Seeskin , Michael Steffan , Brian Geistwhite , Maggie Yarbrough , Michael P. Chen , David Yankey , Yi Mu , Chalanda S. Smith , Tammy A. Santibanez , James A. Singleton , Holly A. Hill , Cassandra Pingali
We conducted exploratory data analyses of the National Immunization Survey-Child COVID Module (NIS-CCM). NIS-CCM is a random digit dialing survey of parents and guardians of 6-month- through 17-year-old children. We conducted latent class analysis to identify different population segments of children according to combinations of parental/guardian intent, attitudes, and behaviors regarding their children's COVID vaccinations. We analyzed data collected between October 2021 and April 2023. The latent class model variables with the greatest variation in conditional probabilities across latent classes included vaccination status, intent to vaccinate, and confidence in the safety of COVID vaccine. The latent classes included one with vaccinated children despite low confidence in vaccine safety and one with unvaccinated children despite high confidence in vaccine safety and high vaccination intent. The latent class that increased the most in size over the period studied was the class most hesitant to vaccination. We further analyzed demographic and environmental characteristics associated with membership in different latent classes using multinomial logistic regression, with the goal of informing strategies to increase vaccination coverage with different population segments. Socioeconomic status and race/ethnicity were associated with latent class membership. Specific social and environmental factors, such as having many family and friends' children vaccinated for COVID and receiving a provider's recommendation for vaccination were associated with more favorable-to-vaccination class membership. While the exploratory analyses do not establish causal relationships, the research shows the value of latent class analysis with high-quality survey data to inform further research on strategies to increase vaccination coverage.
{"title":"Using latent class analysis of survey data to explore parent behaviors and attitudes regarding children's COVID vaccinations","authors":"Zachary H. Seeskin , Michael Steffan , Brian Geistwhite , Maggie Yarbrough , Michael P. Chen , David Yankey , Yi Mu , Chalanda S. Smith , Tammy A. Santibanez , James A. Singleton , Holly A. Hill , Cassandra Pingali","doi":"10.1016/j.vaccine.2025.128149","DOIUrl":"10.1016/j.vaccine.2025.128149","url":null,"abstract":"<div><div>We conducted exploratory data analyses of the National Immunization Survey-Child COVID Module (NIS-CCM). NIS-CCM is a random digit dialing survey of parents and guardians of 6-month- through 17-year-old children. We conducted latent class analysis to identify different population segments of children according to combinations of parental/guardian intent, attitudes, and behaviors regarding their children's COVID vaccinations. We analyzed data collected between October 2021 and April 2023. The latent class model variables with the greatest variation in conditional probabilities across latent classes included vaccination status, intent to vaccinate, and confidence in the safety of COVID vaccine. The latent classes included one with vaccinated children despite low confidence in vaccine safety and one with unvaccinated children despite high confidence in vaccine safety and high vaccination intent. The latent class that increased the most in size over the period studied was the class most hesitant to vaccination. We further analyzed demographic and environmental characteristics associated with membership in different latent classes using multinomial logistic regression, with the goal of informing strategies to increase vaccination coverage with different population segments. Socioeconomic status and race/ethnicity were associated with latent class membership. Specific social and environmental factors, such as having many family and friends' children vaccinated for COVID and receiving a provider's recommendation for vaccination were associated with more favorable-to-vaccination class membership. While the exploratory analyses do not establish causal relationships, the research shows the value of latent class analysis with high-quality survey data to inform further research on strategies to increase vaccination coverage.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128149"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128129
V. Sethna , A. Apte , S. Sanghavi , Y. Tang , C. Poonawalla , R. Dhere , G. Dayma , A. Kawade , R. Nerlekar , A. Jadhav , R. Tuttle , W.P. Hausdorff , A. Bavdekar
Background
Reduction in the vaccine serotype (VT) carriage is a surrogate marker of pneumococcal vaccines protection. PNEUMOSIL®, a 10-valent pneumococcal conjugate vaccine (PCV) has been recently introduced in the national immunization program of India in a 2 + 1 schedule. Owing to scarcity of data about impact of PNEUMOSIL® vaccination on VT-carriage, the current study was conducted in Indian children to assess its impact.
Methods
This was a community-based cross-sectional observational study conducted between November 2022–March 2023 in rural areas of Pune, India. The study population included healthy children either fully vaccinated with PNEUMOSIL® 2 + 1 schedule through Universal Immunization Program or PCV-naïve. The vaccinated group was enrolled at least 4 months after receipt of the last PCV dose. Nasopharyngeal swabs were collected upon enrolment using World Health Organization methods in all children to isolate Streptococcus pneumoniae and identify serotypes using a Quellung test. The VT-carriage were compared between PCV-vaccinated and PCV-naïve using univariate and multivariate logistic regression.
Findings
The study enrolled 700 healthy children; 350 children aged 15–20 months previously fully vaccinated with PNEUMOSIL® 2 + 1 schedule through UIP and 350 PCV-naïve children aged 16–21 months. Overall S. pneumoniae carriage in PCV-vaccinated and PCV-naïve groups was 63·1 % (95 % CI 57·9 %-68·2 %) and 66·3 % (95 % CI 61·1 %-71·2 %), respectively (p = 0·384). VT-carriage occurred in 23·4 % (95 % CI 19·1 %-28·2 %) of vaccinated children and 30·9 % (95 % CI 26·1 %-36·0 %) of PCV-naïve participants (24·3 % reduction, p = 0·027). After adjusting for colonization risk factors, PNEUMOSIL® vaccination was associated with 32 % reduction in odds of VT colonization compared with PCV-naïve participants [OR = 0·68; 95 % CI 0·49–0·96].
Interpretation
The observed reduction in VT-carriage amongst Indian children was comparable to that observed with other PCVs that have demonstrated marked declines in disease transmission. These results suggest PNEUMOSIL® could be an effective public health tool in decreasing pneumococcal disease.
{"title":"Nasopharyngeal pneumococcal carriage in Indian children following 10-valent PCV (PNEUMOSIL®) introduction through India's universal immunization program: A post licensure cross-sectional study.","authors":"V. Sethna , A. Apte , S. Sanghavi , Y. Tang , C. Poonawalla , R. Dhere , G. Dayma , A. Kawade , R. Nerlekar , A. Jadhav , R. Tuttle , W.P. Hausdorff , A. Bavdekar","doi":"10.1016/j.vaccine.2025.128129","DOIUrl":"10.1016/j.vaccine.2025.128129","url":null,"abstract":"<div><h3>Background</h3><div>Reduction in the vaccine serotype (VT) carriage is a surrogate marker of pneumococcal vaccines protection. PNEUMOSIL®, a 10-valent pneumococcal conjugate vaccine (PCV) has been recently introduced in the national immunization program of India in a 2 + 1 schedule. Owing to scarcity of data about impact of PNEUMOSIL® vaccination on VT-carriage, the current study was conducted in Indian children to assess its impact.</div></div><div><h3>Methods</h3><div>This was a community-based cross-sectional observational study conducted between November 2022–March 2023 in rural areas of Pune, India. The study population included healthy children either fully vaccinated with PNEUMOSIL® 2 + 1 schedule through Universal Immunization Program or PCV-naïve. The vaccinated group was enrolled at least 4 months after receipt of the last PCV dose. Nasopharyngeal swabs were collected upon enrolment using World Health Organization methods in all children to isolate <em>Streptococcus pneumoniae</em> and identify serotypes using a Quellung test. The VT-carriage were compared between PCV-vaccinated and PCV-naïve using univariate and multivariate logistic regression.</div></div><div><h3>Findings</h3><div>The study enrolled 700 healthy children; 350 children aged 15–20 months previously fully vaccinated with PNEUMOSIL® 2 + 1 schedule through UIP and 350 PCV-naïve children aged 16–21 months. Overall <em>S. pneumoniae</em> carriage in PCV-vaccinated and PCV-naïve groups was 63·1 % (95 % CI 57·9 %-68·2 %) and 66·3 % (95 % CI 61·1 %-71·2 %), respectively (<em>p</em> = 0·384). VT-carriage occurred in 23·4 % (95 % CI 19·1 %-28·2 %) of vaccinated children and 30·9 % (95 % CI 26·1 %-36·0 %) of PCV-naïve participants (24·3 % reduction, <em>p</em> = 0·027). After adjusting for colonization risk factors, PNEUMOSIL® vaccination was associated with 32 % reduction in odds of VT colonization compared with PCV-naïve participants [OR = 0·68; 95 % CI 0·49–0·96].</div></div><div><h3>Interpretation</h3><div>The observed reduction in VT-carriage amongst Indian children was comparable to that observed with other PCVs that have demonstrated marked declines in disease transmission. These results suggest PNEUMOSIL® could be an effective public health tool in decreasing pneumococcal disease.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128129"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yellow fever (YF) is a mosquito-borne viral haemorrhagic disease that remains endemic in parts of South America and Africa. Although there is a safe and effective vaccine that has been available for over 75 years, YF remains a public health problem in areas with endemic as well as sporadic transmission. Immune responses elicited by natural infection with yellow fever virus and vaccination are marked by production of neutralizing antibodies. Serological cross-reactivity exhibited by flaviviruses poses challenges to the diagnostic tests for detection of YF-specific antibodies. The most specific plaque reduction neutralization test (PRNT) is considered the “gold standard” test for detecting and measuring the neutralizing antibodies. This study was undertaken to develop and validate in-house PRNT50 test for measurement of YF specific neutralizing antibodies. We validated PRNT50 test using different parameters including specificity, linearity, precision, accuracy and robustness. The YF PRNT50 assay was shown to be specific, robust, precise and accurate. Thus, we have proven suitability of this assay for evaluation of neutralizing antibodies in response to YF vaccination in case of natural infections.
{"title":"Plaque reduction neutralization test (PRNT50) for the detection of anti-yellow fever antibodies from clinical samples","authors":"Parikshit Tyagi , Milan Ganguly , Satyaprasad Manney , Kuntinath Wadkar , Nilesh Ingle , Sunil Gairola , Rajeev Dhere , Giulia Lapini , Paolo Cantaloni","doi":"10.1016/j.vaccine.2025.128151","DOIUrl":"10.1016/j.vaccine.2025.128151","url":null,"abstract":"<div><div>Yellow fever (YF) is a mosquito-borne viral haemorrhagic disease that remains endemic in parts of South America and Africa. Although there is a safe and effective vaccine that has been available for over 75 years, YF remains a public health problem in areas with endemic as well as sporadic transmission. Immune responses elicited by natural infection with yellow fever virus and vaccination are marked by production of neutralizing antibodies. Serological cross-reactivity exhibited by flaviviruses poses challenges to the diagnostic tests for detection of YF-specific antibodies. The most specific plaque reduction neutralization test (PRNT) is considered the “gold standard” test for detecting and measuring the neutralizing antibodies. This study was undertaken to develop and validate in-house PRNT<sub>50</sub> test for measurement of YF specific neutralizing antibodies. We validated PRNT<sub>50</sub> test using different parameters including specificity, linearity, precision, accuracy and robustness. The YF PRNT<sub>50</sub> assay was shown to be specific, robust, precise and accurate. Thus, we have proven suitability of this assay for evaluation of neutralizing antibodies in response to YF vaccination in case of natural infections.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128151"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128157
Shincy M. Ramakrishnan , Feroze A. Ganaie , Vandana Govindan , Akhila M Mavupadi , Geetha Nagaraj , Anil Chandra , Vani Rajashekaraiah , K.L. Ravikumar
Measuring immune responses to pneumococcal vaccines is crucial for evaluating their impact and efficacy. Herein, we measured type-specific IgG antibody levels before and after immunization with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 51 healthy Indian adults using WHO-ELISA. Baseline geometric mean concentrations were adequate (≥1.3 μg/mL) against ∼83% of the capsule polysaccharide (CPS) types, with notably higher levels for serotypes 14, 15B, 19A, and 33F. Post-vaccination, IgG antibody levels significantly increased for 22 of 23 CPS types, with medians ranging from 2.3 to 57.8 μg/mL. The highest geometric mean fold rise (∼6 to 9-fold) was observed for CPS types 7F, 9N, 8, and 33F. The findings highlight the capability of PPSV23 to strengthen protective immunity against pneumococcal disease in Indian adults, advocating for its continued use. Further studies are needed to optimize vaccination strategies and evaluate the functional activity of induced antibodies.
{"title":"Pneumococcal baseline IgG antibody levels and immune response to 23-valent pneumococcal polysaccharide vaccine among Indian adults","authors":"Shincy M. Ramakrishnan , Feroze A. Ganaie , Vandana Govindan , Akhila M Mavupadi , Geetha Nagaraj , Anil Chandra , Vani Rajashekaraiah , K.L. Ravikumar","doi":"10.1016/j.vaccine.2025.128157","DOIUrl":"10.1016/j.vaccine.2025.128157","url":null,"abstract":"<div><div>Measuring immune responses to pneumococcal vaccines is crucial for evaluating their impact and efficacy. Herein, we measured type-specific IgG antibody levels before and after immunization with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 51 healthy Indian adults using WHO-ELISA. Baseline geometric mean concentrations were adequate (≥1.3 μg/mL) against ∼83% of the capsule polysaccharide (CPS) types, with notably higher levels for serotypes 14, 15B, 19A, and 33F. Post-vaccination, IgG antibody levels significantly increased for 22 of 23 CPS types, with medians ranging from 2.3 to 57.8 μg/mL. The highest geometric mean fold rise (∼6 to 9-fold) was observed for CPS types 7F, 9N, 8, and 33F. The findings highlight the capability of PPSV23 to strengthen protective immunity against pneumococcal disease in Indian adults, advocating for its continued use. Further studies are needed to optimize vaccination strategies and evaluate the functional activity of induced antibodies.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128157"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128147
Sandeepan Das , Feroza Begum , Subhadip Ghora , Upasana Ray
Dengue virus remains a significant public health concern in tropical and subtropical regions, with vaccine development facing considerable challenges. A major obstacle is antibody-dependent enhancement (ADE), which limits the clinical translation of vaccine candidates utilizing structural proteins as antigens. To circumvent this issue, we designed mRNA-based vaccine candidates targeting the non-structural protein NS1. Given the propensity of NS1's C-terminal region to induce autoantibodies, we focused on N-terminal half of the protein. One antigen comprised a truncated NS1 (amino acids 1–270), while the second was chimeric featuring truncated Dengue NS1 at the N-terminus and the C-terminal region (amino acids 271–352) of Japanese encephalitis virus (JEV) NS1. Additionally, a lysine-to-arginine substitution at position 116 (Lys116Arg) was introduced to mitigate the risk of endothelial cell autoantibody formation. All mRNAs successfully expressed their respective antigens in Huh7 cells, with both full-length NS1 and chimeric NS1 being secreted, whereas the truncated NS1 remained intracellular. mRNAs were encapsulated in lipid nanoparticles (LNPs) and administered to Balb/C mice. The native and the chimeric antigens elicited immune responses, with IgG profiling indicating a predominant IgG2a response and displayed reduction in viral load in virus challenge studies. Notably, sera from mice immunized with chimeric NS1 did not cross-react with endothelial cells, unlike sera from those immunized with full-length NS1 and neutralized the entry of NS1 in liver cells efficiently. These findings suggest that the chimeric NS1 antigen is both immunogenic and less likely to trigger autoantibody-mediated adverse effects, highlighting its potential as a safer therapeutic dengue vaccine.
{"title":"Engineered dengue virus NS1 mRNA-lipid nanoparticle induces therapeutic IgG production that lacks autoantibody activity and neutralizes NS1 entry in liver cells","authors":"Sandeepan Das , Feroza Begum , Subhadip Ghora , Upasana Ray","doi":"10.1016/j.vaccine.2025.128147","DOIUrl":"10.1016/j.vaccine.2025.128147","url":null,"abstract":"<div><div>Dengue virus remains a significant public health concern in tropical and subtropical regions, with vaccine development facing considerable challenges. A major obstacle is antibody-dependent enhancement (ADE), which limits the clinical translation of vaccine candidates utilizing structural proteins as antigens. To circumvent this issue, we designed mRNA-based vaccine candidates targeting the non-structural protein NS1. Given the propensity of NS1's C-terminal region to induce autoantibodies, we focused on N-terminal half of the protein. One antigen comprised a truncated NS1 (amino acids 1–270), while the second was chimeric featuring truncated Dengue NS1 at the N-terminus and the C-terminal region (amino acids 271–352) of Japanese encephalitis virus (JEV) NS1. Additionally, a lysine-to-arginine substitution at position 116 (Lys116Arg) was introduced to mitigate the risk of endothelial cell autoantibody formation. All mRNAs successfully expressed their respective antigens in Huh7 cells, with both full-length NS1 and chimeric NS1 being secreted, whereas the truncated NS1 remained intracellular. mRNAs were encapsulated in lipid nanoparticles (LNPs) and administered to Balb/C mice. The native and the chimeric antigens elicited immune responses, with IgG profiling indicating a predominant IgG2a response and displayed reduction in viral load in virus challenge studies. Notably, sera from mice immunized with chimeric NS1 did not cross-react with endothelial cells, unlike sera from those immunized with full-length NS1 and neutralized the entry of NS1 in liver cells efficiently. These findings suggest that the chimeric NS1 antigen is both immunogenic and less likely to trigger autoantibody-mediated adverse effects, highlighting its potential as a safer therapeutic dengue vaccine.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128147"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The introduction of prophylactic HPV vaccination has significantly reduced vaccine-type HPV infections and is reshaping the landscape of cervical cancer prevention. As vaccinated cohorts enter screening age, understanding the genotype-specific risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) is critical for adapting screening strategies.
Aim
To compare HPV genotype-specific detection rates of histologically confirmed CIN2+ between vaccinated and unvaccinated women in Denmark's Trial23 cohort, with over seven years of follow-up.
Method
This population-based cohort study included 15,668 women born in 1994 who were offered HPV vaccination with the 4-valent vaccine in 2008 and entered Danish screening age in 2017 In our cohort, 95 % were vaccinated and 5 % were unvaccinated. The primary endpoints of this study were HPV-type-specific incident CIN2+ cases. The first histological biopsy sample diagnosed with CIN2+ in 2017–2023 was retrieved for HPV genotyping with the Seegene Allplex HPV28. Cox proportional hazards models estimated hazard ratios (HRs) for CIN2+ outcomes by hierarchically grouped HPV genotypes.
Results
Among vaccinated women, the incidence of CIN2+ was 5.3 per 1000 person-years, compared to 12.1 per 1000 person-years in unvaccinated women (HR: 0.44; 95 % CI: 0.34–0.57). Vaccination was associated with a 95 % reduction in HPV16/18-related CIN2+ (HR: 0.05; 95 % CI: 0.03–0.09). A similar, but non-significant, trend of a 32 % risk of CIN2+ for HPV31/33/45/52/58 was found, with an adjusted HR of 0.68 (95 % CI: 0.43–1.09). For CIN2+ associated with other high-risk HPV types, the HR was 0.70 (95 % CI 0.35–1.37).
Conclusion
HPV16/18 vaccination reduced the risk of HPV16/18-related CIN2+ lesions, but a substantial burden remained from non-vaccine high-risk types. The substantial protection against HPV16/18-related CIN2+ and the consequential shift in HPV genotype distribution of CIN2+ among vaccinated women underline the need for adaptation of screening strategies.
{"title":"Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2+ from childhood vaccinated women: The Trial23 cohort study","authors":"Mette Hartmann Nonboe , George Napolitano , Jeppe Bennekou Schroll , Berit Andersen , Sanne Christiansen , Anna Poulsgaard Frandsen , Helle Pedersen , Elsebeth Lynge , Jesper Bonde , Estrid Høgdall","doi":"10.1016/j.vaccine.2025.128142","DOIUrl":"10.1016/j.vaccine.2025.128142","url":null,"abstract":"<div><h3>Background</h3><div>The introduction of prophylactic HPV vaccination has significantly reduced vaccine-type HPV infections and is reshaping the landscape of cervical cancer prevention. As vaccinated cohorts enter screening age, understanding the genotype-specific risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) is critical for adapting screening strategies.</div></div><div><h3>Aim</h3><div>To compare HPV genotype-specific detection rates of histologically confirmed CIN2+ between vaccinated and unvaccinated women in Denmark's Trial23 cohort, with over seven years of follow-up.</div></div><div><h3>Method</h3><div>This population-based cohort study included 15,668 women born in 1994 who were offered HPV vaccination with the 4-valent vaccine in 2008 and entered Danish screening age in 2017 In our cohort, 95 % were vaccinated and 5 % were unvaccinated. The primary endpoints of this study were HPV-type-specific incident CIN2+ cases. The first histological biopsy sample diagnosed with CIN2+ in 2017–2023 was retrieved for HPV genotyping with the Seegene Allplex HPV28. Cox proportional hazards models estimated hazard ratios (HRs) for CIN2+ outcomes by hierarchically grouped HPV genotypes.</div></div><div><h3>Results</h3><div>Among vaccinated women, the incidence of CIN2+ was 5.3 per 1000 person-years, compared to 12.1 per 1000 person-years in unvaccinated women (HR: 0.44; 95 % CI: 0.34–0.57). Vaccination was associated with a 95 % reduction in HPV16/18-related CIN2+ (HR: 0.05; 95 % CI: 0.03–0.09). A similar, but non-significant, trend of a 32 % risk of CIN2+ for HPV31/33/45/52/58 was found, with an adjusted HR of 0.68 (95 % CI: 0.43–1.09). For CIN2+ associated with other high-risk HPV types, the HR was 0.70 (95 % CI 0.35–1.37).</div></div><div><h3>Conclusion</h3><div>HPV16/18 vaccination reduced the risk of HPV16/18-related CIN2+ lesions, but a substantial burden remained from non-vaccine high-risk types. The substantial protection against HPV16/18-related CIN2+ and the consequential shift in HPV genotype distribution of CIN2+ among vaccinated women underline the need for adaptation of screening strategies.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128142"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128159
Natasha Rodrigues de Oliveira , Mara Andrade Colares Maia , Tiffany Thurow Bunde , Ana Carolina Kurz Pedra , Jady Duarte Nogueira , Laura de Vargas Maiocchi , Amilton Clair Pinto Seixas Neto , Livia Maria Faim , Mariana Antao Cavalcanti Pizani , Paulina Consuelo Morales Arancibia , Thaís Larré Oliveira Bohn , Odir Antônio Dellagostin
Leptospirosis is a widespread zoonosis caused by Leptospira spp. New vaccine strategies are being explored to enhance both the magnitude and duration of protection. In this study, we developed a novel recombinant vaccine formulation, using the Pyrococcus abyssi exosome complex to present immunogenic regions of key Leptospira antigens (LigANI, LigBrep, and LipL32). A co-expression vector containing the P. abyssi exosome proteins fused to the three Leptospira antigens was constructed, generating the EXOLEP (EXOsome + LEPtospira) multivalent complex, and the polyproteins were expressed in Escherichia coli. The stability of EXOLEP was confirmed through in vitro and in vivo assays, demonstrating remarkable resistance, remaining stable at temperatures up to 100 °C and extended shelf life. In hamster model, a hybrid EXOLEP formulation (EXOLEP Copenhageni + Leptospira bacterin from serovar Canicola) provided 80–100 % protection (P < 0.05) against Leptospira serovars Copenhageni and Canicola. Additionally, the hybrid formulation induced a balanced Th1/Th2 immune response, evidenced by upregulation of IFN-γ, TNF-α, IL-10, and TGF-β, along with significant levels (P < 0.05) of IgG1 and IgG2/3 isotypes against all Leptospira antigens. The formulation maintained its efficacy after one year of storage at 4 °C. These results suggest that the EXOLEP hybrid is a promising, cost-effective, and scalable candidate for veterinary leptospirosis vaccines.
{"title":"A self-assembled Pirococcus abyssi exosome complex displaying outer membrane proteins of Leptospira interrogans elicits protective immunity against leptospirosis","authors":"Natasha Rodrigues de Oliveira , Mara Andrade Colares Maia , Tiffany Thurow Bunde , Ana Carolina Kurz Pedra , Jady Duarte Nogueira , Laura de Vargas Maiocchi , Amilton Clair Pinto Seixas Neto , Livia Maria Faim , Mariana Antao Cavalcanti Pizani , Paulina Consuelo Morales Arancibia , Thaís Larré Oliveira Bohn , Odir Antônio Dellagostin","doi":"10.1016/j.vaccine.2025.128159","DOIUrl":"10.1016/j.vaccine.2025.128159","url":null,"abstract":"<div><div>Leptospirosis is a widespread zoonosis caused by <em>Leptospira spp.</em> New vaccine strategies are being explored to enhance both the magnitude and duration of protection. In this study, we developed a novel recombinant vaccine formulation, using the <em>Pyrococcus abyssi</em> exosome complex to present immunogenic regions of key <em>Leptospira</em> antigens (LigANI, LigBrep, and LipL32). A co-expression vector containing the <em>P. abyssi</em> exosome proteins fused to the three <em>Leptospira</em> antigens was constructed, generating the EXOLEP (EXOsome + LEPtospira) multivalent complex, and the polyproteins were expressed in <em>Escherichia coli.</em> The stability of EXOLEP was confirmed through <em>in vitro</em> and <em>in vivo</em> assays, demonstrating remarkable resistance, remaining stable at temperatures up to 100 °C and extended shelf life. In hamster model, a hybrid EXOLEP formulation (EXOLEP Copenhageni + <em>Leptospira</em> bacterin from serovar Canicola) provided 80–100 % protection (<em>P</em> < 0.05) against <em>Leptospira</em> serovars Copenhageni and Canicola. Additionally, the hybrid formulation induced a balanced Th1/Th2 immune response, evidenced by upregulation of IFN-γ, TNF-α, IL-10, and TGF-β, along with significant levels (<em>P</em> < 0.05) of IgG1 and IgG2/3 isotypes against all <em>Leptospira</em> antigens. The formulation maintained its efficacy after one year of storage at 4 °C. These results suggest that the EXOLEP hybrid is a promising, cost-effective, and scalable candidate for veterinary leptospirosis vaccines.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128159"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128155
Fredrikke Dam Larsen , Anna Karina Juhl , Lisa Loksø Dietz , Henrik Nielsen , Nina Breinholt Stærke , Isik Somuncu Johansen , Lothar Wiese , Thomas Benfield , Jacob Bodilsen , Vibeke Klastrup , Susan Olaf Lindvig , Line Dahlerup Rasmussen , Lene Surland Knudsen , Martin Tolstrup , Lars Jørgen Østergaard , Jens Lundgren , Ole Schmeltz Søgaard , Carsten Schade Larsen , On behalf of the ENFORCE Study Group
Introduction: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of severe COVID-19 infection. Their immunosuppressive treatment may lead to attenuated vaccine responses. In this study, we assessed the impact of specific immunosuppressive treatments on the immunogenicity of primary SARS-CoV-2 vaccination as well as booster vaccinations in IMID patients.
Material and methods: We included participants with IMID from the Danish ENFORCE cohort with baseline sampling prior to SARS-CoV-2 vaccination. Participants were followed for two years, with scheduled visits prior to vaccine dose 2, day 90, 180, 365 and 730 as well as before and after each booster dose. At all visits, seroconversion rates and quantitative SARS-CoV-2 Spike IgG antibody levels were assessed. Vaccine hyporesponsiveness, defined as <2log10 increase in SARS-CoV-2 Spike IgG levels from baseline, was evaluated at day 90 and again after the first booster.
Results: We included 282 patients with IMID and 482 immunocompetent controls. At day 90, patients with IMID treated with anti-CD20 antibodies or fingolimod exhibited markedly reduced seroconversion rates (27 % and 60 %, respectively, vs 100 % for controls), significantly lower antibody levels (2251 AU/mL [95 % CI: 888–5703] and 1743 AU/mL [95 % CI:784–3873] vs 186,308 AU/mL [95 % CI, 171366–202,552]) and higher odds of vaccine hyporesponsiveness (odds ratio (OR) = 67.5 [95 % CI, 25.4–179.7] and 82.5 [95 % CI, 29.6–196.3]). This impaired response persisted throughout the follow-up period, and anti-CD20 antibodies and fingolimod treated patients never reached antibody titers comparable to day 90 titers in controls, despite repeated booster vaccinations.
Conclusion: Anti-CD20 antibody treatment and fingolimod severely impair humoral vaccine responses in IMID patients. In contrast, IMID patients treated with Methotrexate, TNF-alpha inhibitors, or other immunosuppressants mounted efficient vaccine responses. These findings support that tailored vaccine schedules with early and frequent boosters are crucial to protect this high-risk population.
Clinical Trial registration: EudraCT no, 2020–006003-42, NVK no. 1–10–72-337-20.
{"title":"Immunogenicity of SARS-CoV-2 primary vaccination and boosters in patients with immune-mediated inflammatory diseases: Impact of immunosuppressive therapy","authors":"Fredrikke Dam Larsen , Anna Karina Juhl , Lisa Loksø Dietz , Henrik Nielsen , Nina Breinholt Stærke , Isik Somuncu Johansen , Lothar Wiese , Thomas Benfield , Jacob Bodilsen , Vibeke Klastrup , Susan Olaf Lindvig , Line Dahlerup Rasmussen , Lene Surland Knudsen , Martin Tolstrup , Lars Jørgen Østergaard , Jens Lundgren , Ole Schmeltz Søgaard , Carsten Schade Larsen , On behalf of the ENFORCE Study Group","doi":"10.1016/j.vaccine.2025.128155","DOIUrl":"10.1016/j.vaccine.2025.128155","url":null,"abstract":"<div><div>Introduction: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of severe COVID-19 infection. Their immunosuppressive treatment may lead to attenuated vaccine responses. In this study, we assessed the impact of specific immunosuppressive treatments on the immunogenicity of primary SARS-CoV-2 vaccination as well as booster vaccinations in IMID patients.</div><div>Material and methods: We included participants with IMID from the Danish ENFORCE cohort with baseline sampling prior to SARS-CoV-2 vaccination. Participants were followed for two years, with scheduled visits prior to vaccine dose 2, day 90, 180, 365 and 730 as well as before and after each booster dose. At all visits, seroconversion rates and quantitative SARS-CoV-2 Spike IgG antibody levels were assessed. Vaccine hyporesponsiveness, defined as <2log<sub>10</sub> increase in SARS-CoV-2 Spike IgG levels from baseline, was evaluated at day 90 and again after the first booster.</div><div>Results: We included 282 patients with IMID and 482 immunocompetent controls. At day 90, patients with IMID treated with anti-CD20 antibodies or fingolimod exhibited markedly reduced seroconversion rates (27 % and 60 %, respectively, vs 100 % for controls), significantly lower antibody levels (2251 AU/mL [95 % CI: 888–5703] and 1743 AU/mL [95 % CI:784–3873] vs 186,308 AU/mL [95 % CI, 171366–202,552]) and higher odds of vaccine hyporesponsiveness (odds ratio (OR) = 67.5 [95 % CI, 25.4–179.7] and 82.5 [95 % CI, 29.6–196.3]). This impaired response persisted throughout the follow-up period, and anti-CD20 antibodies and fingolimod treated patients never reached antibody titers comparable to day 90 titers in controls, despite repeated booster vaccinations.</div><div>Conclusion: Anti-CD20 antibody treatment and fingolimod severely impair humoral vaccine responses in IMID patients. In contrast, IMID patients treated with Methotrexate, TNF-alpha inhibitors, or other immunosuppressants mounted efficient vaccine responses. These findings support that tailored vaccine schedules with early and frequent boosters are crucial to protect this high-risk population.</div><div>Clinical Trial registration: EudraCT no, 2020–006003-42, NVK no. 1–10–72-337-20.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"73 ","pages":"Article 128155"},"PeriodicalIF":4.5,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.vaccine.2025.128137
Joyce Pijpers , Annika van Roon , Susan van den Hof , Ruben van Gaalen , Hester de Melker , Susan Hahné
Background
Recently, the number of measles and pertussis cases increased worldwide, including in the Netherlands. As schools are important in transmission of several vaccine-preventable diseases, we systematically assessed childhood vaccination coverage in the Netherlands among primary school children by birth cohort for all school denominations.
Methods
We linked nationwide vaccination data with sociodemographic registries for children born 2013–2020 attending primary school on 01-10-2024. Vaccination status for MMR (at 14 months), DTaP-IPV (at (2)3–5-11 months), and DTaP-booster (at 4 years) was retrieved from the immunisation register. Vaccination coverage was stratified by school denomination, birth year and sociodemographic characteristics. Poisson regression assessed independent associations between denomination and vaccination uptake.
Results
MMR and DTaP-IPV coverage was high (>94 %) in general, Catholic, Protestant, collaborative, and other schools, but lower in Anthroposophical (78 % MMR, 77 % DTaP-IPV), Islamic (74 % MMR, 75 % DTaP-IPV), and Orthodox Protestant schools (57 % MMR, 58 % DTaP-IPV). DTaP-IPV booster coverage was lower than the primary series, ranging from 50 % (Orthodox Protestant) to 88 % (Catholic/Protestant). Primary coverage remained stable for most denominations (overall 95 %) but declined at Islamic schools (MMR: 87 % to 59 %, DTaP-IPV: 88 % to 60 %) and moderately at Orthodox Protestant schools (MMR: 60 % to 54 %, DTaP-IPV: 60 % to 55 %), while coverage at Anthroposophical schools fluctuated (MMR: range 76–81 %, DTaP-IPV: range 74–79 %). Adjusting for sociodemographic variables had little impact.
Conclusions
Although most unvaccinated children attend schools with high coverage, clustering at Orthodox Protestant, Anthroposophical, and increasingly Islamic schools poses ongoing outbreak risks. Further research on vaccination barriers, drivers, and the role of social networks is needed to better understand vaccination decisions.
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