NPJ VaccinesPub Date : 2024-12-19DOI: 10.1038/s41541-024-01043-3
Paolla Beatriz Almeida Pinto, Julia Timis, Kantinan Chuensirikulchai, Qin Hui Li, Hsueh Han Lu, Erin Maule, Michael Nguyen, Rúbens Prince Dos Santos Alves, Shailendra Kumar Verma, Fernanda Ana-Sosa-Batiz, Kristen Valentine, Sara Landeras-Bueno, Kenneth Kim, Kathryn Hastie, Erica Ollmann Saphire, Ada Alves, Annie Elong Ngono, Sujan Shresta
{"title":"Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron.","authors":"Paolla Beatriz Almeida Pinto, Julia Timis, Kantinan Chuensirikulchai, Qin Hui Li, Hsueh Han Lu, Erin Maule, Michael Nguyen, Rúbens Prince Dos Santos Alves, Shailendra Kumar Verma, Fernanda Ana-Sosa-Batiz, Kristen Valentine, Sara Landeras-Bueno, Kenneth Kim, Kathryn Hastie, Erica Ollmann Saphire, Ada Alves, Annie Elong Ngono, Sujan Shresta","doi":"10.1038/s41541-024-01043-3","DOIUrl":"10.1038/s41541-024-01043-3","url":null,"abstract":"<p><p>The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice. S, N, and S + N vaccines all elicited polyfunctional CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses and provided short-term cross-protection against Beta and Omicron BA.2 variants, but only co-immunization with S + N vaccines provided long-term protection against Omicron BA.2. Depletion of CD4<sup>+</sup> and CD8<sup>+</sup> T cells reduced the long-term efficacy, demonstrating a crucial role for T cells in the durability of protection. These findings underscore the potential to enhance long-lived protection against SARS-CoV-2 variants by combining S and N antigens in next-generation COVID-19 vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"252"},"PeriodicalIF":6.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-12-17DOI: 10.1038/s41541-024-01021-9
Young Chan Kim, Yasunori Watanabe, Lücke Arlen-Celina, Xiyong Song, Raquel de Oliveira Souza, Robert Stass, Sasha R Azar, Shannan L Rossi, Carla Claser, Beate Mareike Kümmerer, Max Crispin, Thomas A Bowden, Juha T Huiskonen, Arturo Reyes-Sandoval
{"title":"Immunogenic recombinant Mayaro virus-like particles present natively assembled glycoprotein.","authors":"Young Chan Kim, Yasunori Watanabe, Lücke Arlen-Celina, Xiyong Song, Raquel de Oliveira Souza, Robert Stass, Sasha R Azar, Shannan L Rossi, Carla Claser, Beate Mareike Kümmerer, Max Crispin, Thomas A Bowden, Juha T Huiskonen, Arturo Reyes-Sandoval","doi":"10.1038/s41541-024-01021-9","DOIUrl":"10.1038/s41541-024-01021-9","url":null,"abstract":"<p><p>Virus-like particles (VLPs) are an established vaccine platform and can be strong immunogens capable of eliciting both humoral and cellular immune responses against a range of pathogens. Here, we show by cryo-electron microscopy that VLPs of Mayaro virus, which contain envelope glycoproteins E1-E2 and capsid, exhibit an architecture that closely resembles native virus. In contrast to monomeric and soluble envelope 2 (E2) glycoprotein, both VLPs as well as the adenovirus and modified vaccinia virus Ankara (MVA) vaccine platforms expressing the equivalent envelope glycoproteins E1-E2, and capsid induced highly neutralising antibodies after immunisation. The levels of neutralising antibodies elicited by the viral-vectored vaccines of structural proteins and VLPs increased significantly upon boosting. Immunisation of Mayaro virus VLPs in mice with or without an adjuvant (poly:IC) yielded similar levels of neutralising antibodies suggesting that the VLPs may be used for immunisation without the need for an adjuvant. A single or two doses of non-adjuvanted 5 µg of MAYV VLP vaccination provided significant protection against viremia and MAYV-induced foot swelling in the C57BL/6 mouse challenge model. MAYV VLPs represent a non-infectious vaccine candidate, which may constitute a complementary option for future immunisation strategies against this important emerging alphavirus.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"243"},"PeriodicalIF":6.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-12-09DOI: 10.1038/s41541-024-01027-3
Eriberto Noel Natali, Alexander Horst, Patrick Meier, Victor Greiff, Mario Nuvolone, Lmar Marie Babrak, Katja Fink, Enkelejda Miho
{"title":"Publisher Correction: The dengue-specific immune response and antibody identification with machine learning.","authors":"Eriberto Noel Natali, Alexander Horst, Patrick Meier, Victor Greiff, Mario Nuvolone, Lmar Marie Babrak, Katja Fink, Enkelejda Miho","doi":"10.1038/s41541-024-01027-3","DOIUrl":"10.1038/s41541-024-01027-3","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"242"},"PeriodicalIF":6.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-12-06DOI: 10.1038/s41541-024-01040-6
Naveen Yadav, Anya C Kalata, Rebekah A Reynolds, Andrew Raappana, D Noah Sather, Sean C Murphy
{"title":"Identifying Plasmodium P36 and P52 antigens for coadministration with circumsporozoite protein to enhance vaccine efficacy.","authors":"Naveen Yadav, Anya C Kalata, Rebekah A Reynolds, Andrew Raappana, D Noah Sather, Sean C Murphy","doi":"10.1038/s41541-024-01040-6","DOIUrl":"10.1038/s41541-024-01040-6","url":null,"abstract":"<p><p>Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from the inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP. Co-administration of P36 and/or P52 with CSP achieved 80-100% sterile protection in mice, compared to only 7-30% protection for each individual antigen. P36 and P52 vaccination induced murine CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses, but not antibody responses. This study adds P36 and P52 as promising vaccine antigens that may enhance the protection achieved by CSP vaccination.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"241"},"PeriodicalIF":6.9,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11624287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-12-05DOI: 10.1038/s41541-024-01038-0
Andrew T DeLaitsch, Jennifer R Keeffe, Harry B Gristick, Juliet A Lee, Wenge Ding, Weimin Liu, Ashwin N Skelly, George M Shaw, Beatrice H Hahn, Pamela J Björkman
{"title":"Neutralizing antibodies elicited in macaques recognize V3 residues on altered conformations of HIV-1 Env trimer.","authors":"Andrew T DeLaitsch, Jennifer R Keeffe, Harry B Gristick, Juliet A Lee, Wenge Ding, Weimin Liu, Ashwin N Skelly, George M Shaw, Beatrice H Hahn, Pamela J Björkman","doi":"10.1038/s41541-024-01038-0","DOIUrl":"10.1038/s41541-024-01038-0","url":null,"abstract":"<p><p>Eliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing antibodies elicited in non-human primates by priming with an engineered V3-targeting SOSIP Env immunogen and boosting with increasingly native-like SOSIP Envs derived from different strain backgrounds. Structures of Env trimers in complex with these antibodies revealed V3 targeting, but on conformational states of Env distinct from the typical closed, prefusion trimeric SOSIP structure. Env trimers bound by Ab1456 adopted conformations resembling CD4-bound open Env states in the absence of soluble CD4, whereas trimers bound by Ab1271 exhibited a trimer apex-altered conformation to accommodate antibody binding. The finding that elicited antibodies cross-neutralized by targeting altered, non-closed, prefusion Env trimer conformations provides important information about Env dynamics that is relevant for HIV-1 vaccine design aimed at raising antibodies to desired epitopes on closed pre-fusion Env trimers.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"240"},"PeriodicalIF":6.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-12-02DOI: 10.1038/s41541-024-01025-5
Lorenzo Argante, Ottavia Prunas, Duccio Medini, Ellen Ypma
{"title":"Modeling the persistence of 4CMenB vaccine protection against real world meningococcal B disease in adolescents.","authors":"Lorenzo Argante, Ottavia Prunas, Duccio Medini, Ellen Ypma","doi":"10.1038/s41541-024-01025-5","DOIUrl":"10.1038/s41541-024-01025-5","url":null,"abstract":"<p><p>The efficacy of the four-component 4CMenB vaccine is measured through the serum bactericidal antibody (SBA) assay on four meningococcal B (MenB) indicator strains. However, they are not epidemiologically relevant for disease, thus the real-world persistence of 4CMenB protection remains uncertain. Several mathematical models of waning immunity were fitted on longitudinal SBA data from persistence studies in adolescents, with up to eight years follow-up after 4CMenB priming vaccination. The best model was used to predict protection from indicator strains. MenB typing data from the United States were used to integrate antigen-level curves and predict the persistence of protection from real-world MenB strains, considering synergies between antigens. Models show that protection and its evolution varied by antigen and that 4CMenB likely elicits antibody-producing long-lived plasma cells. 4CMenB protection from real-world MenB disease persisted at 61.5% four years post-priming and 70.5% four years post-booster. This evidence could support decision-making on adolescent immunization programs.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"239"},"PeriodicalIF":6.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11612355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-11-29DOI: 10.1038/s41541-024-01028-2
Ratnadeep Mukherjee, Linn Margrethe Eggesbø, Asia-Sophia Wolf, Ingrid Fadum Kjønstad, Guri Solum, Anthony Ravussin, Sabin Bhandari, Anna Hayman Robertson, Per Magnus, Lill Trogstad, Anja Bråthen Kristoffersen, Unni Cecilie Nygaard, Siri Mjaaland
{"title":"Mass cytometry reveals cellular correlates of immune response heterogeneity to SARS-CoV-2 vaccination in the elderly.","authors":"Ratnadeep Mukherjee, Linn Margrethe Eggesbø, Asia-Sophia Wolf, Ingrid Fadum Kjønstad, Guri Solum, Anthony Ravussin, Sabin Bhandari, Anna Hayman Robertson, Per Magnus, Lill Trogstad, Anja Bråthen Kristoffersen, Unni Cecilie Nygaard, Siri Mjaaland","doi":"10.1038/s41541-024-01028-2","DOIUrl":"10.1038/s41541-024-01028-2","url":null,"abstract":"<p><p>Heterogeneity in vaccine response, particularly in vulnerable populations like the elderly, represents a significant public health challenge. We conducted an in-depth examination of immune cell profiles before and after SARS-CoV-2 vaccination utilizing mass cytometry in a cohort of healthy Norwegian seniors (65-80 years). We have demonstrated that higher pre-vaccination frequencies of CD27<sup>+</sup>IgD<sup>-</sup> class-switched memory B cells and subsets of CD27<sup>-</sup>CD24<sup>+</sup>CD38<sup>+</sup> transitional B cells were associated with a robust vaccine response. Post-vaccination, high responders exhibited increased frequencies of IFN-γ<sup>+</sup>CD4<sup>+</sup> T cells with antigen recall and a concurrent decrease in CCR6(+) T<sub>H</sub> cell subset frequencies compared to low responders. The presence of a γδ T cell subset displaying polyfunctional cytokine responses was also associated with better vaccine response in the elderly. This in-depth profiling sheds light on inherent differences in immune cell frequencies and functions that may offer insights for targeted vaccination strategies in older populations.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"238"},"PeriodicalIF":6.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-11-27DOI: 10.1038/s41541-024-01030-8
Nisa Ya, Heidi Auerswald, Sothy Touch, Saraden In, Chanvannak Yun, Pisey Thai, Sotheary Sann, Borita Heng, Chanthy Leng, Veasna Duong, Yik Sing Peng, Sowath Ly, Tineke Cantaert
{"title":"Evaluation of one year immunity following rabies post-exposure prophylaxis in dog bite cases.","authors":"Nisa Ya, Heidi Auerswald, Sothy Touch, Saraden In, Chanvannak Yun, Pisey Thai, Sotheary Sann, Borita Heng, Chanthy Leng, Veasna Duong, Yik Sing Peng, Sowath Ly, Tineke Cantaert","doi":"10.1038/s41541-024-01030-8","DOIUrl":"10.1038/s41541-024-01030-8","url":null,"abstract":"<p><p>Rabies remains a global health threat despite being preventable with post-exposure prophylaxis (PEP). This study assessed one-year humoral and T cell immunity in PEP recipients of the Insitut Pasteur du Cambodge (IPC) regimen, recommended by WHO. We analyzed rabies virus (RABV) neutralizing antibodies (nAbs) and T cell responses at baseline, 7 and 14 days, 6 and 12 months after PEP. A total of 148 patients were included, with 78 bitten by confirmed RABV-positive dogs receiving PEP and equine rabies immunoglobulins (eRIG), and 70 bitten by RABV-negative dogs receiving only PEP. Fourteen days after PEP, all but two individuals seroconverted for nAbs ( ≥ 0.5 IU/mL) with 87% maintaining this response even after 12 months. Interleukin-4 (IL-4) and interferon-gamma (IFN-γ)-secreting T cells were significantly elevated after 14 days and sustained for one year. No differences were observed between the RABV-exposed and -unexposed groups. This study demonstrates robust one-year immunity after IPC PEP.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"237"},"PeriodicalIF":6.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-11-27DOI: 10.1038/s41541-024-01029-1
Abdullah A Al-Omari, Katherine W Cook, Peter Symonds, Anne Skinner, Alissa Wright, Yaling Zhu, Vincent L Coble, Omar J Mohammed, Ruhul H Choudhury, Nazim Uddin, Priscilla Ranglani, Adrian Parry, Sally E Adams, Geoffrey M Lynn, Lindy G Durrant, Victoria A Brentville
{"title":"Modi-2 a vaccine stimulating CD4 responses to homocitrullinated self epitopes as therapy for solid cancers.","authors":"Abdullah A Al-Omari, Katherine W Cook, Peter Symonds, Anne Skinner, Alissa Wright, Yaling Zhu, Vincent L Coble, Omar J Mohammed, Ruhul H Choudhury, Nazim Uddin, Priscilla Ranglani, Adrian Parry, Sally E Adams, Geoffrey M Lynn, Lindy G Durrant, Victoria A Brentville","doi":"10.1038/s41541-024-01029-1","DOIUrl":"10.1038/s41541-024-01029-1","url":null,"abstract":"<p><p>Stresses within the tumour microenvironment can mediate post-translational modifications of self-proteins. Homocitrullination is the conversion of lysine to homocitrulline which generates neoepitopes and bypasses self-tolerance. In this study a vaccine targeting homocitrullinated antigens was assessed for stimulation of anti-tumour immunity. Peptides that bind HLA are often hydrophobic which can complicate large scale manufacture and solubility. Here we demonstrate the self-assembling nanoparticle technology (SNAPvax<sup>TM</sup>) to co-deliver four homocitrullinated peptides and adjuvant in nanoparticles of a precise size and composition as a vaccine (\"Modi-2\") that is optimized for manufacturing ease and T cell induction. Strong T cell responses and anti-tumour immunity in mouse tumour models was stimulated against against B16 melanoma (p = 0.0113), CT26 colorectal cancer (p < 0.0001) and 4T1 breast cancer (p = 0.0090). We demonstrate that human lung, colorectal, breast and prostate tumours express the Modi-2 target antigens and propose the Modi-2 vaccine has potential for translation into clinic in several cancer indications.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"236"},"PeriodicalIF":6.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ VaccinesPub Date : 2024-11-25DOI: 10.1038/s41541-024-01024-6
Leslie van der Fits, Rineke de Jong, Karin Dijkman, Marjolein Heemskerk-van der Meer, Lisanne Tettero, Judith Bonsing, Sophie van Oort, Jan Serroyen, Marianke van Schie, Norbert Stockhofe-Zurwieden, Benoit Callendret, Roland Zahn
{"title":"Ad26.RSV.preF completely protects calves from severe respiratory disease induced by bovine RSV challenge.","authors":"Leslie van der Fits, Rineke de Jong, Karin Dijkman, Marjolein Heemskerk-van der Meer, Lisanne Tettero, Judith Bonsing, Sophie van Oort, Jan Serroyen, Marianke van Schie, Norbert Stockhofe-Zurwieden, Benoit Callendret, Roland Zahn","doi":"10.1038/s41541-024-01024-6","DOIUrl":"10.1038/s41541-024-01024-6","url":null,"abstract":"<p><p>Vaccination with Ad26.RSV.preF, an Adenoviral serotype 26 vector encoding RSV F protein stabilized in its prefusion conformation, has previously shown to be immunogenic and protective in RSV seropositive adults and immunogenic in seropositive infants. Human and bovine RSV (bRSV) are genetically highly related and share many aspects of pathogenesis, epidemiology and clinical manifestations at young age. As such, infection of calves with bRSV represents a clinically relevant model with high translational value, enabling preclinical evaluation of Ad26.RSV.preF vaccine efficacy in seronegative young animals. Immunization of young calves with Ad26.RSV.preF induced antibodies neutralizing both human and bovine RSV as well as RSV-specific cellular responses. After bRSV challenge, placebo immunized calves showed viral replication in the respiratory tract, and developed fever and lethargy accompanied with severe respiratory distress, resulting in pre-termination of 7/8 calves. In contrast, all Ad26.RSV.preF immunized calves completed the study with only mild clinical symptoms, strongly and significantly diminished viral loads in nasopharynx and lungs, and only minimal lung pathology. Thus, Ad26.RSV.preF is immunogenic in young calves and efficacious in a stringent heterologous bRSV challenge model, demonstrating induction of broadly protective immunity against severe disease.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"235"},"PeriodicalIF":6.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11589129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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