NPJ Vaccines最新文献

{"title":"Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction.","authors":"Eigo Kawahara, Kota Senpuku, Yoshino Kawaguchi, Shinya Yamamoto, Koubun Yasuda, Etsushi Kuroda, Noriko Ouji-Sageshima, Toshihiro Ito, Toshiro Hirai, Takehiko Shibata, Yasuo Yoshioka","doi":"10.1038/s41541-024-00987-w","DOIUrl":"10.1038/s41541-024-00987-w","url":null,"abstract":"<p><p>The G protein expressed on the surface of respiratory syncytial virus (RSV) is important for adhesion to host cells and as a vaccine target antigen. The corresponding vaccines can effectively eliminate RSV. However, they exacerbate pulmonary immunopathology including eosinophilic infiltration in the lungs after an RSV challenge in animal models, raising concerns about enhanced respiratory disease (ERD); thus, approaches that mitigate these effects are urgently needed. Herein, we aimed to examine the mechanisms of G protein vaccine-induced ERD in mice, using recombinant G protein as a vaccine antigen. After the RSV challenge, G protein-vaccinated mice exhibited lung weight gain, lung tissue damage, and increased infiltration of eosinophils, neutrophils, and CD4⁺ T cells into the lungs. We set lung weight gain as the endpoint for ERD and examined the impact of each infiltrating cell on lung weight gain. We observed that CD4⁺ T cells, but not eosinophils or neutrophils, that infiltrate the lungs are responsible for lung weight gain. In addition, T helper 2 cell-mediated IL-13 induced mucin hypersecretion and lung weight gain. Mucin hypersecretion may contribute to weight gain in the lungs. In conclusion, our results indicate a novel mechanism of G protein vaccine-induced ERD via IL-13 and mucin hypersecretion, which could lead to the development of safe G protein vaccines and the elucidation of the causes of ERD associated with other vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"187"},"PeriodicalIF":6.9,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406665","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}

{"title":"Filovirus vaccines as a response paradigm for emerging infectious diseases.","authors":"Andrea Marzi, Heinz Feldmann","doi":"10.1038/s41541-024-00985-y","DOIUrl":"10.1038/s41541-024-00985-y","url":null,"abstract":"<p><p>Nowadays, filovirus vaccine development may be seen as a paradigm for our response capabilities to emerging and re-emerging infectious diseases. Specifically, the West African Ebola virus disease (EVD) epidemic accelerated countermeasure licensure for several vaccine and therapeutic products. Those products have been successfully used to control EVD outbreaks in Central Africa over the past years. This positive development, however, has not yet reached beyond EVD. Therefore, it is pertinent to increase our efforts in the development of countermeasures for other human pathogenic members of the family Filoviridae as they continue to threaten public health in Sub-Saharan Africa. This review article summarizes the current filovirus vaccines in preclinical macaque studies and human clinical trials and discusses the most promising recent advancements.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"186"},"PeriodicalIF":6.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406664","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}

{"title":"Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections.","authors":"Amin Alirezaylavasani, Linda Gail Skeie, Ingrid Marie Egner, Adity Chopra, Tuva Børresdatter Dahl, Christian Prebensen, John Torgils Vaage, Bente Halvorsen, Fridtjof Lund-Johansen, Kristian Tonby, Dag Henrik Reikvam, Birgitte Stiksrud, Jan Cato Holter, Anne Ma Dyrhol-Riise, Ludvig A Munthe, Hassen Kared","doi":"10.1038/s41541-024-00972-3","DOIUrl":"10.1038/s41541-024-00972-3","url":null,"abstract":"<p><p>The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm³). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"185"},"PeriodicalIF":6.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392165","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}

{"title":"Potent neutralization of SARS-CoV-2 variants by RBD nanoparticle and prefusion-stabilized spike immunogens.","authors":"Marcos C Miranda, Elizabeth Kepl, Mary Jane Navarro, Chengbo Chen, Max Johnson, Kaitlin R Sprouse, Cameron Stewart, Anne Palser, Adian Valdez, Deleah Pettie, Claire Sydeman, Cassandra Ogohara, John C Kraft, Minh Pham, Michael Murphy, Sam Wrenn, Brooke Fiala, Rashmi Ravichandran, Daniel Ellis, Lauren Carter, Davide Corti, Paul Kellam, Kelly Lee, Alexandra C Walls, David Veesler, Neil P King","doi":"10.1038/s41541-024-00982-1","DOIUrl":"10.1038/s41541-024-00982-1","url":null,"abstract":"<p><p>We previously described a two-component protein nanoparticle vaccine platform that displays 60 copies of the SARS-CoV-2 spike protein RBD (RBD-NP). The vaccine, when adjuvanted with AS03, was shown to elicit robust neutralizing antibody and CD4 T cell responses in Phase I/II clinical trials, met its primary co-endpoints in a Phase III trial, and has been licensed by multiple regulatory authorities under the brand name SKYCovione^TM. Here we characterize the biophysical properties, stability, antigenicity, and immunogenicity of RBD-NP immunogens incorporating mutations from the B.1.351 (β) and P.1 (γ) variants of concern (VOCs) that emerged in 2020. We also show that the RBD-NP platform can be adapted to the Omicron strains BA.5 and XBB.1.5. We compare β and γ variant and E484K point mutant nanoparticle immunogens to the nanoparticle displaying the Wu-1 RBD, as well as to soluble prefusion-stabilized (HexaPro) spike trimers harboring VOC-derived mutations. We find the properties of immunogens based on different SARS-CoV-2 variants can differ substantially, which could affect the viability of variant vaccine development. Introducing stabilizing mutations in the linoleic acid binding site of the RBD-NPs resulted in increased physical stability compared to versions lacking the stabilizing mutations without deleteriously affecting immunogenicity. The RBD-NP immunogens and HexaPro trimers, as well as combinations of VOC-based immunogens, elicited comparable levels of neutralizing antibodies against distinct VOCs. Our results demonstrate that RBD-NP-based vaccines can elicit neutralizing antibody responses against SARS-CoV-2 variants and can be rapidly designed and stabilized, demonstrating the potential of two-component RBD-NPs as a platform for the development of broadly protective coronavirus vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"184"},"PeriodicalIF":6.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392163","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}

{"title":"Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines.","authors":"Teresa Hauguel, Amy Sharma, Emily Mastrocola, Susan Lowry, Mohan S Maddur, Cheng Hui Hu, Swati Rajput, Allison Vitsky, Shambhunath Choudhary, Balasubramanian Manickam, Ivna De Souza, Yana Chervona, Raquel Munoz Moreno, Charisse Abdon, Larissa Falcao, Kristin Tompkins, Deanne Illenberger, Rachel Smith, Fanyu Meng, Shuai Shi, Kari Sweeney Efferen, Victoria Markiewicz, Cinthia Umemoto, Jianfang Hu, Wei Chen, Ingrid Scully, Cynthia M Rohde, Annaliesa S Anderson, Pirada Suphaphiphat Allen","doi":"10.1038/s41541-024-00980-3","DOIUrl":"10.1038/s41541-024-00980-3","url":null,"abstract":"<p><p>Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4⁺ T cell responses, and HA-specific CD8⁺ T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ⁺ CD4⁺ T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"183"},"PeriodicalIF":6.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392164","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}

{"title":"Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection.","authors":"Elena N Atochina-Vasserman, Lisa C Lindesmith, Carmen Mirabelli, Nathan A Ona, Erin K Reagan, Paul D Brewer-Jensen, Xiomara Mercado-Lopez, Hamna Shahnawaz, Jaclynn A Meshanni, Ishana Baboo, Michael L Mallory, Mark R Zweigart, Samantha R May, Barbara L Mui, Ying K Tam, Christiane E Wobus, Ralph S Baric, Drew Weissman","doi":"10.1038/s41541-024-00976-z","DOIUrl":"10.1038/s41541-024-00976-z","url":null,"abstract":"<p><p>Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"182"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361858","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}

{"title":"DNA vaccines against GPRC5D synergize with PD-1 blockade to treat multiple myeloma.","authors":"Praveen Neeli, Perry Ayn Mayson A Maza, Dafei Chai, Dan Zhao, Xen Ping Hoi, Keith Syson Chan, Ken H Young, Yong Li","doi":"10.1038/s41541-024-00979-w","DOIUrl":"10.1038/s41541-024-00979-w","url":null,"abstract":"<p><p>Multiple myeloma (MM), a hematological malignancy of the bone marrow, remains largely incurable. The orphan G protein-coupled receptor, GPRC5D, which is uniquely expressed in plasma cells and highly expressed in MM, is a compelling candidate for immunotherapy. In this study, we investigated the efficacy of a combination of DNA vaccine encoding mouse GPRC5D and PD-1 blockade in preventing and treating MM using the 5TGM1 murine model of MM. The mouse vaccine alone was effective in preventing myeloma growth but required PD-1 antibodies to inhibit established MM tumors. We next evaluated the prophylactic and therapeutic efficacy of a nanoplasmid vector encoding human GPRC5D in several murine syngeneic tumor models. Similar results for tumor inhibition were observed, as human GPRC5D-specific T cells and antibodies were induced by DNA vaccines. Taken together, these findings underscore the potential of GPRC5D-targeted DNA vaccines as versatile platforms for the treatment and prevention of MM.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"180"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361859","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}

{"title":"Interventions for the control of Crimean-Congo hemorrhagic fever and tick vectors.","authors":"José de la Fuente, Srikant Ghosh, Laetitia Lempereur, Aura Garrison, Hein Sprong, Cesar Lopez-Camacho, Christine Maritz-Olivier, Marinela Contreras, Alberto Moraga-Fernández, Dennis A Bente","doi":"10.1038/s41541-024-00970-5","DOIUrl":"10.1038/s41541-024-00970-5","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease associated with its principal tick vector, Hyalomma spp. with increasing fatal incidence worldwide. Accordingly, CCHF is a World Health Organization-prioritized disease with the absence of effective preventive interventions and approved vaccines or effective treatments. This perspective raised from a multidisciplinary gap analysis considering a One Health approach beneficial for human and animal health and the environment exploring international collaborations, gaps and recommendations.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"181"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361860","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}

{"title":"Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates.","authors":"Kanika Vanshylla, Jeroen Tolboom, Kathryn E Stephenson, Karin Feddes-de Boer, Annemiek Verwilligen, Sietske Karla Rosendahl Huber, Lucy Rutten, Hanneke Schuitemaker, Roland C Zahn, Dan H Barouch, Frank Wegmann","doi":"10.1038/s41541-024-00974-1","DOIUrl":"10.1038/s41541-024-00974-1","url":null,"abstract":"<p><p>The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"179"},"PeriodicalIF":6.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351002","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}

{"title":"Development of T follicular helper cell-independent nanoparticle vaccines for SARS-CoV-2 or HIV-1 by targeting ICOSL.","authors":"Yongli Zhang, Achun Chen, Daiying Li, Quyu Yuan, Airu Zhu, Jieyi Deng, Yalin Wang, Jie Liu, Chaofeng Liang, Wenjie Li, Qiannan Fang, Jiatong Xie, Xiantao Zhang, Xu Zhang, Yiwen Zhang, Ran Chen, Ting Pan, Hui Zhang, Xin He","doi":"10.1038/s41541-024-00971-4","DOIUrl":"https://doi.org/10.1038/s41541-024-00971-4","url":null,"abstract":"<p><p>T helper cells, particularly T follicular helper (T_FH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from T_FH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in T_FH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of T_FH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"176"},"PeriodicalIF":6.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351000","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}