NPJ Vaccines最新文献_第7页

Genomic tailoring of autogenous poultry vaccines to reduce Campylobacter from farm to fork. 基因组定制自体禽类疫苗，减少从农场到餐桌的弯曲杆菌。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-12 DOI: 10.1038/s41541-024-00879-z

Jessica K Calland, Maiju E Pesonen, Jai Mehat, Ben Pascoe, David J Haydon, Jose Lourenco, Barbara Lukasiewicz, Evangelos Mourkas, Matthew D Hitchings, Roberto M La Ragione, Philip Hammond, Timothy S Wallis, Jukka Corander, Samuel K Sheppard

{"title":"Genomic tailoring of autogenous poultry vaccines to reduce Campylobacter from farm to fork.","authors":"Jessica K Calland, Maiju E Pesonen, Jai Mehat, Ben Pascoe, David J Haydon, Jose Lourenco, Barbara Lukasiewicz, Evangelos Mourkas, Matthew D Hitchings, Roberto M La Ragione, Philip Hammond, Timothy S Wallis, Jukka Corander, Samuel K Sheppard","doi":"10.1038/s41541-024-00879-z","DOIUrl":"10.1038/s41541-024-00879-z","url":null,"abstract":"Campylobacter is a leading cause of food-borne gastroenteritis worldwide, linked to the consumption of contaminated poultry meat. Targeting this pathogen at source, vaccines for poultry can provide short-term caecal reductions in Campylobacter numbers in the chicken intestine. However, this approach is unlikely to reduce Campylobacter in the food chain or human incidence. This is likely as vaccines typically target only a subset of the high genomic strain diversity circulating among chicken flocks, and rapid evolution diminishes vaccine efficacy over time. To address this, we used a genomic approach to develop a whole-cell autogenous vaccine targeting isolates harbouring genes linked to survival outside of the host. We hyper-immunised a whole major UK breeder farm to passively target offspring colonisation using maternally-derived antibody. Monitoring progeny, broiler flocks revealed a near-complete shift in the post-vaccination Campylobacter population with an ~50% reduction in isolates harbouring extra-intestinal survival genes and a significant reduction of Campylobacter cells surviving on the surface of meat. Based on these findings, we developed a logistic regression model that predicted that vaccine efficacy could be extended to target 65% of a population of clinically relevant strains. Immuno-manipulation of poultry microbiomes towards less harmful commensal isolates by competitive exclusion, has major potential for reducing pathogens in the food production chain.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311312","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}

引用次数: 0

Safety and efficacy of C. muridarum vaccines adjuvanted with CpG-1826 and four concentrations of Montanide-ISA-720-VG. 用 CpG-1826 和四种浓度的 Montanide-ISA-720-VG 佐剂接种鼠疫疫苗的安全性和有效性。

IF 6.9 1区医学

NPJ Vaccines Pub Date : 2024-06-10 DOI: 10.1038/s41541-024-00880-6

Anatoli Slepenkin, Sukumar Pal, Amy Rasley, Matthew A Coleman, Luis M de la Maza

{"title":"Safety and efficacy of C. muridarum vaccines adjuvanted with CpG-1826 and four concentrations of Montanide-ISA-720-VG.","authors":"Anatoli Slepenkin, Sukumar Pal, Amy Rasley, Matthew A Coleman, Luis M de la Maza","doi":"10.1038/s41541-024-00880-6","DOIUrl":"10.1038/s41541-024-00880-6","url":null,"abstract":"It is recommended that the adjuvant Montanide ISA 720 VG be used at a concentration of 70% v/v. At this concentration, Montanide causes at the site of immunization a local granuloma that can last for several weeks. To determine the safety and protective efficacy of a Chlamydia muridarum MOMP vaccine, formulated with CpG-1826 and four different concentrations of Montanide (70%, 50%, 30% and 10%), BALB/c (H-2d) female mice were immunized twice intramuscularly. Local reactogenicity was significant for vaccines formulated with 70% or 50% Montanide but not for those inoculated with 30% or 10% Montanide. Robust humoral and cell mediated memory immune responses were elicited by the 70%, 50% and 30% Montanide formulations. Mice were challenged intranasally with 104 C. muridarum inclusion forming units (IFU). Based on changes in body weight, lungs's weight and number of IFU recovered, mice vaccinated with the 70%, 50% and 30% Montanide formulations were significantly protected, but not mice receiving 10% Montanide. To conclude, we recommend the 30% Montanide concentration to be tested in humans and animal models to determine its safety and efficacy, in comparison to the 70% Montanide concentration currently used. The 30% Montanide formulation could significantly facilitate licensing of this adjuvant for human use.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301136","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}

引用次数: 0

T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector. 抗 HPV 免疫肿瘤治疗慢病毒载体诱导和重塑的 T 细胞免疫。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-10 DOI: 10.1038/s41541-024-00894-0

Ingrid Fert, Laëtitia Douguet, Benjamin Vesin, Fanny Moncoq, Amandine Noirat, Pierre Authié, Sylvain Ciret, Fabien Le Chevalier, Catherine Blanc, Yakov Vitrenko, Pierre Charneau, Laleh Majlessi, François Anna

{"title":"T-cell immunity induced and reshaped by an anti-HPV immuno-oncotherapeutic lentiviral vector.","authors":"Ingrid Fert, Laëtitia Douguet, Benjamin Vesin, Fanny Moncoq, Amandine Noirat, Pierre Authié, Sylvain Ciret, Fabien Le Chevalier, Catherine Blanc, Yakov Vitrenko, Pierre Charneau, Laleh Majlessi, François Anna","doi":"10.1038/s41541-024-00894-0","DOIUrl":"10.1038/s41541-024-00894-0","url":null,"abstract":"We recently developed an immuno-oncotherapy against human papillomavirus (HPV)-induced tumors based on a lentiviral vector encoding the Early E6 and E7 oncoproteins of HPV16 and HPV18 genotypes, namely \"Lenti-HPV-07\". The robust and long-lasting anti-tumor efficacy of Lenti-HPV-07 is dependent on CD8+ T-cell induction and remodeling of the tumor microenvironment. Here, we first established that anti-vector immunity induced by Lenti-HPV-07 prime has no impact on the efficacy of a homologous boost to amplify anti-HPV T-cell immunity. To longitudinally monitor the evolution of the T-cell repertoire generated after the prime, homologous or heterologous boost with Lenti-HPV-07, we tracked T-cell clonotypes by deep sequencing of T-Cell Receptor (TCR) variable β and α chain mRNA, applied to whole peripheral blood cells (PBL) and a T cell population specific of an immunodominant E7HPV16 epitope. We observed a hyper-expansion of clonotypes post prime, accompanied by increased frequencies of HPV-07-specific T cells. Additionally, there was a notable diversification of clonotypes post boost in whole PBL, but not in the E7HPV16-specific T cells. We then demonstrated that the effector functions of such Lenti-HPV-07-induced T cells synergize with anti-checkpoint inhibitory treatments by systemic administration of anti-TIM3 or anti-NKG2A monoclonal antibodies. While Lenti-HPV-07 is about to enter a Phase I/IIa clinical trial, these results will help better elucidate its mode of action in immunotherapy against established HPV-mediated malignancies.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301137","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}

引用次数: 0

Multivalent mRNA-DTP vaccines are immunogenic and provide protection from Bordetella pertussis challenge in mice. 多价 mRNA-DTP 疫苗具有免疫原性，可保护小鼠免受百日咳博德特氏菌感染。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-10 DOI: 10.1038/s41541-024-00890-4

M Allison Wolf, Joanne M O'Hara, Graham J Bitzer, Elisabeth Narayanan, Dylan T Boehm, Justin R Bevere, Megan A DeJong, Jesse M Hall, Ting Y Wong, Samantha Falcone, Cailin E Deal, Angelene Richards, Shannon Green, Brenda Nguyen, Emily King, Clinton Ogega, Lisa Russo, Emel Sen-Kilic, Obadiah Plante, Sunny Himansu, Mariette Barbier, Andrea Carfi, F Heath Damron

{"title":"Multivalent mRNA-DTP vaccines are immunogenic and provide protection from Bordetella pertussis challenge in mice.","authors":"M Allison Wolf, Joanne M O'Hara, Graham J Bitzer, Elisabeth Narayanan, Dylan T Boehm, Justin R Bevere, Megan A DeJong, Jesse M Hall, Ting Y Wong, Samantha Falcone, Cailin E Deal, Angelene Richards, Shannon Green, Brenda Nguyen, Emily King, Clinton Ogega, Lisa Russo, Emel Sen-Kilic, Obadiah Plante, Sunny Himansu, Mariette Barbier, Andrea Carfi, F Heath Damron","doi":"10.1038/s41541-024-00890-4","DOIUrl":"10.1038/s41541-024-00890-4","url":null,"abstract":"Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301135","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}

引用次数: 0

Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial. 哥斯达黎加人乳头瘤病毒疫苗试验中不同变体对二价人乳头瘤病毒疫苗的长期交叉保护作用存在差异。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-08 DOI: 10.1038/s41541-024-00896-y

Jaimie Z Shing, Carolina Porras, Maísa Pinheiro, Rolando Herrero, Allan Hildesheim, Danping Liu, Mitchell H Gail, Byron Romero, John T Schiller, Michael Zúñiga, Sambit Mishra, Laurie Burdette, Kristine Jones, John Schussler, Rebeca Ocampo, Jianwen Fang, Zhiwei Liu, Douglas R Lowy, Sabrina H Tsang, Ana Cecilia Rodríguez, Mark Schiffman, Cameron B Haas, Loretto J Carvajal, Jalen R Brown, Aimée R Kreimer, Lisa Mirabello

{"title":"Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial.","authors":"Jaimie Z Shing, Carolina Porras, Maísa Pinheiro, Rolando Herrero, Allan Hildesheim, Danping Liu, Mitchell H Gail, Byron Romero, John T Schiller, Michael Zúñiga, Sambit Mishra, Laurie Burdette, Kristine Jones, John Schussler, Rebeca Ocampo, Jianwen Fang, Zhiwei Liu, Douglas R Lowy, Sabrina H Tsang, Ana Cecilia Rodríguez, Mark Schiffman, Cameron B Haas, Loretto J Carvajal, Jalen R Brown, Aimée R Kreimer, Lisa Mirabello","doi":"10.1038/s41541-024-00896-y","DOIUrl":"10.1038/s41541-024-00896-y","url":null,"abstract":"The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = -34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293604","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}

引用次数: 0

Vaccination with Mincle agonist UM-1098 and mycobacterial antigens induces protective Th1 and Th17 responses. 用 Mincle 激动剂 UM-1098 和分枝杆菌抗原接种疫苗可诱导 Th1 和 Th17 保护性反应。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-06 DOI: 10.1038/s41541-024-00897-x

Viktoria Rungelrath, Mushtaq Ahmed, Linda Hicks, Shannon M Miller, Kendal T Ryter, Kyle Montgomery, George Ettenger, Alexander Riffey, Walid M Abdelwahab, Shabaana Abdul Khader, Jay T Evans

{"title":"Vaccination with Mincle agonist UM-1098 and mycobacterial antigens induces protective Th1 and Th17 responses.","authors":"Viktoria Rungelrath, Mushtaq Ahmed, Linda Hicks, Shannon M Miller, Kendal T Ryter, Kyle Montgomery, George Ettenger, Alexander Riffey, Walid M Abdelwahab, Shabaana Abdul Khader, Jay T Evans","doi":"10.1038/s41541-024-00897-x","DOIUrl":"10.1038/s41541-024-00897-x","url":null,"abstract":"Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the top infectious killers in the world. The only licensed vaccine against TB, Bacille Calmette-Guérin (BCG), provides variable protection against pulmonary TB, especially in adults. Hence, novel TB vaccine approaches are urgently needed. Both Th1 and Th17 responses are necessary for protection against TB, yet effective adjuvants and vaccine delivery systems for inducing robust Th1 and Th17 immunity are lacking. Herein we describe a synthetic Mincle agonist, UM-1098, and a silica nanoparticle delivery system that drives Th1/Th17 responses to Mtb antigens. Stimulation of human peripheral blood mononuclear cells (hPBMCs) with UM-1098 induced high levels of Th17 polarizing cytokines IL-6, IL-1β, IL-23 as well as IL-12p70, IL-4 and TNF-α in vitro. PBMCs from both C57BL/6 and BALB/c mice responded with a similar cytokine pattern in vitro and in vivo. Importantly, intramuscular (I.M.) vaccination with UM-1098-adjuvanted TB antigen M72 resulted in significantly higher antigen-specific IFN-γ and IL-17A levels in C57BL/6 wt mice than Mincle KO mice. Vaccination of C57BL/6 wt mice with immunodominant Mtb antigens ESAT6/Ag85B or M72 resulted in predominantly Th1 and Th17 responses and induced antigen-specific serum antibodies. Notably, in a virulent Mtb challenge model, vaccination with UM-1098 adjuvanted ESAT6/Ag85B or M72 significantly reduced lung bacterial burden when compared with unvaccinated mice and protection occurred in the absence of pulmonary inflammation. These data demonstrate that the synthetic Mincle agonist UM-1098 induces strong Th1 and Th17 immunity after vaccination with Mtb antigens and provides protection against Mtb infection in mice.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11156909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284331","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}

引用次数: 0

Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines. 鉴定基于腺病毒的 COVID 19 疫苗中的交叉反应性 T 细胞反应。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-05 DOI: 10.1038/s41541-024-00895-z

Joshua Gardner, Simon Timothy Abrams, Cheng-Hock Toh, Alan L Parker, Charlotte Lovatt, Phillip L R Nicolson, Steve P Watson, Sophie Grice, Luisa Hering, Munir Pirmohamed, Dean J Naisbitt

{"title":"Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines.","authors":"Joshua Gardner, Simon Timothy Abrams, Cheng-Hock Toh, Alan L Parker, Charlotte Lovatt, Phillip L R Nicolson, Steve P Watson, Sophie Grice, Luisa Hering, Munir Pirmohamed, Dean J Naisbitt","doi":"10.1038/s41541-024-00895-z","DOIUrl":"10.1038/s41541-024-00895-z","url":null,"abstract":"Vaccination has proven to be a valuable tool to combat SARS-CoV-2. However, reports of rare adverse reactions such as thrombosis/thrombocytopenia syndrome after ChAdOx1 nCoV-19 vaccination have caused scientific, public and media concern. ChAdOx1 was vectorised from the Y25 chimpanzee adenovirus, which was selected due to low human seroprevalence to circumvent pre-existing immunity. In this study, we aimed to explore patterns of T-cell activation after SARS-CoV-2 COVID-19 vaccine exposure in vitro using PBMCs collected from pre-pandemic ChAdOx1 nCoV-19 naïve healthy donors (HDs), and ChAdOx1 nCoV-19 and Pfizer vaccinated controls. PBMCs were assessed for T-cell proliferation using the lymphocyte transformation test (LTT) following exposure to SARS-CoV-2 COVID-19 vaccines. Cytokine analysis was performed via intracellular cytokine staining, ELISpot assay and LEGENDplex immunoassays. T-cell assays performed in pre-pandemic vaccine naïve HDs, revealed widespread lymphocyte stimulation after exposure to ChAdOx1 nCoV-19 (95%), ChAdOx-spike (90%) and the Ad26.COV2. S vaccine, but not on exposure to the BNT162b2 vaccine. ICS analysis demonstrated that CD4+ CD45RO+ memory T-cells are activated by ChAdOx1 nCoV-19 in vaccine naïve HDs. Cytometric immunoassays showed ChAdOx1 nCoV-19 exposure was associated with the release of proinflammatory and cytotoxic molecules, such as IFN-γ, IL-6, perforin, granzyme B and FasL. These studies demonstrate a ubiquitous T-cell response to ChAdOx1 nCoV-19 and Ad26.COV2. S in HDs recruited prior to the SARS-CoV-2 pandemic, with T-cell stimulation also identified in vaccinated controls. This may be due to underlying T-cell cross-reactivity with prevalent human adenoviruses and further study will be needed to identify T-cell epitopes involved.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11153626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262549","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}

引用次数: 0

Long-term trial of protection provided by adenovirus-vectored vaccine expressing the PPRV H protein. 表达 PPRV H 蛋白的腺病毒载体疫苗提供保护的长期试验。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-06-03 DOI: 10.1038/s41541-024-00892-2

Karin E Darpel, Amanda Corla, Anna Stedman, Fiona Bellamy, John Flannery, Paulina Rajko-Nenow, Claire Powers, Steve Wilson, Bryan Charleston, Michael D Baron, Carrie Batten

{"title":"Long-term trial of protection provided by adenovirus-vectored vaccine expressing the PPRV H protein.","authors":"Karin E Darpel, Amanda Corla, Anna Stedman, Fiona Bellamy, John Flannery, Paulina Rajko-Nenow, Claire Powers, Steve Wilson, Bryan Charleston, Michael D Baron, Carrie Batten","doi":"10.1038/s41541-024-00892-2","DOIUrl":"10.1038/s41541-024-00892-2","url":null,"abstract":"A recombinant, replication-defective, adenovirus-vectored vaccine expressing the H surface glycoprotein of peste des petits ruminants virus (PPRV) has previously been shown to protect goats from challenge with wild-type PPRV at up to 4 months post vaccination. Here, we present the results of a longer-term trial of the protection provided by such a vaccine, challenging animals at 6, 9, 12 and 15 months post vaccination. Vaccinated animals developed high levels of anti-PPRV H protein antibodies, which were virus-neutralising, and the level of these antibodies was maintained for the duration of the trial. The vaccinated animals were largely protected against overt clinical disease from the challenge virus. Although viral genome was intermittently detected in blood samples, nasal and/or ocular swabs of vaccinated goats post challenge, viral RNA levels were significantly lower compared to unvaccinated control animals and vaccinated goats did not appear to excrete live virus. This protection, like the antibody response, was maintained at the same level for at least 15 months after vaccination. In addition, we showed that animals that have been vaccinated with the adenovirus-based vaccine can be revaccinated with the same vaccine after 12 months and showed an increased anti-PPRV antibody response after this boost vaccination. Such vaccines, which provide a DIVA capability, would therefore be suitable for use when the current live attenuated PPRV vaccines are withdrawn at the end of the ongoing global PPR eradication campaign.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11148195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238302","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}

引用次数: 0

Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge. 显示神经氨酸酶的纳米粒子可激发增强的抗体反应，保护人们免受甲型流感病毒的侵袭。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-05-31 DOI: 10.1038/s41541-024-00891-3

M N Pascha, M Ballegeer, M C Roelofs, L Meuris, I C Albulescu, F J M van Kuppeveld, D L Hurdiss, B J Bosch, T Zeev-Ben-Mordehai, X Saelens, C A M de Haan

{"title":"Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge.","authors":"M N Pascha, M Ballegeer, M C Roelofs, L Meuris, I C Albulescu, F J M van Kuppeveld, D L Hurdiss, B J Bosch, T Zeev-Ben-Mordehai, X Saelens, C A M de Haan","doi":"10.1038/s41541-024-00891-3","DOIUrl":"10.1038/s41541-024-00891-3","url":null,"abstract":"Current Influenza virus vaccines primarily induce antibody responses against variable epitopes in hemagglutinin (HA), necessitating frequent updates. However, antibodies against neuraminidase (NA) can also confer protection against influenza, making NA an attractive target for the development of novel vaccines. In this study, we aimed to enhance the immunogenicity of recombinant NA antigens by presenting them multivalently on a nanoparticle carrier. Soluble tetrameric NA antigens of the N1 and N2 subtypes, confirmed to be correctly folded by cryo-electron microscopy structural analysis, were conjugated to Mi3 self-assembling protein nanoparticles using the SpyTag-SpyCatcher system. Immunization of mice with NA-Mi3 nanoparticles induced higher titers of NA-binding and -inhibiting antibodies and improved protection against a lethal challenge compared to unconjugated NA. Additionally, we explored the co-presentation of N1 and N2 antigens on the same Mi3 particles to create a mosaic vaccine candidate. These mosaic nanoparticles elicited antibody titers that were similar or superior to the homotypic nanoparticles and effectively protected against H1N1 and H3N2 challenge viruses. The NA-Mi3 nanoparticles represent a promising vaccine candidate that could complement HA-directed approaches for enhanced potency and broadened protection against influenza A virus.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183447","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}

引用次数: 0

Neoantigen-augmented iPSC cancer vaccine combined with radiotherapy promotes antitumor immunity in poorly immunogenic cancers. 新抗原增强型 iPSC 癌症疫苗与放疗相结合可促进免疫原性差的癌症患者的抗肿瘤免疫。

IF 9.2 1区医学

NPJ Vaccines Pub Date : 2024-05-31 DOI: 10.1038/s41541-024-00881-5

Kevin Chih-Yang Huang, William Tzu-Liang Chen, Jia-Yi Chen, Chien-Yueh Lee, Chia-Hsin Wu, Chia-Ying Lai, Pei-Chen Yang, Ji-An Liang, An-Cheng Shiau, K S Clifford Chao, Tao-Wei Ke

{"title":"Neoantigen-augmented iPSC cancer vaccine combined with radiotherapy promotes antitumor immunity in poorly immunogenic cancers.","authors":"Kevin Chih-Yang Huang, William Tzu-Liang Chen, Jia-Yi Chen, Chien-Yueh Lee, Chia-Hsin Wu, Chia-Ying Lai, Pei-Chen Yang, Ji-An Liang, An-Cheng Shiau, K S Clifford Chao, Tao-Wei Ke","doi":"10.1038/s41541-024-00881-5","DOIUrl":"10.1038/s41541-024-00881-5","url":null,"abstract":"Although irradiated induced-pluripotent stem cells (iPSCs) as a prophylactic cancer vaccine elicit an antitumor immune response, the therapeutic efficacy of iPSC-based cancer vaccines is not promising due to their insufficient antigenicity and the immunosuppressive tumor microenvironment. Here, we found that neoantigen-engineered iPSC cancer vaccines can trigger neoantigen-specific T cell responses to eradicate cancer cells and increase the therapeutic efficacy of RT in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC). We generated neoantigen-augmented iPSCs (NA-iPSCs) by engineering AAV2 vector carrying murine neoantigens and evaluated their therapeutic efficacy in combination with radiotherapy. After administration of NA-iPSC cancer vaccine and radiotherapy, we found that ~60% of tumor-bearing mice achieved a complete response in microsatellite-stable CRC model. Furthermore, splenocytes from mice treated with NA-iPSC plus RT produced high levels of IFNγ secretion in response to neoantigens and had a greater cytotoxicity to cancer cells, suggesting that the NA-iPSC vaccine combined with radiotherapy elicited a superior neoantigen-specific T-cell response to eradicate cancer cells. The superior therapeutic efficacy of NA-iPSCs engineered by mouse TNBC neoantigens was also observed in the syngeneic immunocompetent TNBC mouse model. We found that the risk of spontaneous lung and liver metastasis was dramatically decreased by NA-iPSCs plus RT in the TNBC animal model. Altogether, these results indicated that autologous iPSC cancer vaccines engineered by neoantigens can elicit a high neoantigen-specific T-cell response, promote tumor regression, and reduce the risk of distant metastasis in combination with local radiotherapy.","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183487","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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