NPJ Vaccines最新文献

{"title":"COVID-19 vaccination atlas using an integrative systems vaccinology approach.","authors":"Wasim Aluísio Prates-Syed, Dennyson Leandro Mathias da Fonseca, Shahab Zaki Pour, Aline Lira, Nelson Cortes, Jaqueline Dinis Queiroz Silva, Evelyn Carvalho, Igor Salerno Filgueiras, Tania Geraldine Churascari Vinces, Lena F Schimke, Lorena C S Chaves, Gerhard Wunderlich, Ricardo Durães-Carvalho, Haroldo Dutra Dias, Hans D Ochs, Niels O S Câmara, Helder I Nakaya, José E Krieger, Otavio Cabral-Marques, Gustavo Cabral-Miranda","doi":"10.1038/s41541-025-01148-3","DOIUrl":"10.1038/s41541-025-01148-3","url":null,"abstract":"<p><p>The COVID-19 vaccinations have played a significant role in controlling the pandemic. To elucidate their impact on the immune system, a COVID-19 vaccination atlas was developed using an integrative systems vaccinology approach. The atlas includes 562 samples from 245 participants, including both healthy individuals and those infected with or without prior vaccination, and covers the administration of five vaccines in different regimens. Key findings include the identification of distinct immune markers that differentiate between vaccine types and infection statuses. We observed that mRNA vaccines induced transient but strong immune responses after booster doses, whereas viral vector vaccines showed sustained immune activation with infection, partially resembling the immune profile exhibited during infection. Heterologous vaccination regimens demonstrated enhanced immune diversification compared to homologous regimens. Finally, we described the immunological landscape of COVID-19 vaccines and vaccines against other pathogens, at the gene-level and in cell population dynamics.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"111"},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209049","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":"Protective efficacy of the pan-fungal vaccine NXT-2 against vulvovaginal candidiasis in a murine model.","authors":"Daniel A Wychrij, Taylor I Chapman, Emily Rayens, Whitney Rabacal, Hubertine M E Willems, Kwadwo O Oworae, Brian M Peters, Karen A Norris","doi":"10.1038/s41541-025-01171-4","DOIUrl":"10.1038/s41541-025-01171-4","url":null,"abstract":"<p><p>Vulvovaginal candidiasis (VVC) is the most common clinical manifestation of candidiasis, affecting 75% of women. Despite high incidence rates, increasing drug resistance, and potential teratogenic effects of current treatments, there are no approved fungal vaccines. Previously, we generated a recombinant 'pan-fungal' vaccine candidate, NXT-2, which demonstrated protection against multiple fungal infections including invasive candidiasis. Here, we evaluated the protective efficacy of NXT-2 against Candida albicans in a murine VVC model. NXT-2 was highly immunogenic, eliciting localized immune responses in the vaginal mucosa. NXT-2 immunized mice had reduced fungal burden and polymorphonuclear neutrophil (PMN) recruitment into the vaginal lumen following C. albicans challenge compared to sham immunized mice. PMNs in the vaginal lumen of NXT-2 immunized mice were associated with C. albicans hyphae, which was absent in controls. NXT-2 immunization reduces vaginal tissue damage and inflammation, while providing antibody-mediated protection, demonstrating the potential of the vaccine for the prevention of VVC.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"112"},"PeriodicalIF":6.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12130295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209050","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":"Single dose VSV-based vaccine protects mice against lethal heterologous Crimean-Congo hemorrhagic fever virus challenge.","authors":"Thomas Tipih, Shanna S Leventhal, Kimberly Meade-White, Matthew Lewis, Trenton Bushmaker, Carl Shaia, Andrea Marzi, Heinz Feldmann, David W Hawman","doi":"10.1038/s41541-025-01164-3","DOIUrl":"10.1038/s41541-025-01164-3","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe, sometimes fatal hemorrhagic fever (CCHF) in humans. Currently, there are no approved therapies against CCHF. In this study we used the recombinant vesicular stomatitis virus (VSV) platform to generate live-attenuated recombinant CCHF vaccine candidates expressing the CCHFV nucleoprotein (NP) and glycoprotein precursor (GPC). As one approach, we utilized the established VSV expressing the full-length Ebola virus glycoprotein (VSV-EBOV) or a truncated version of the EBOV glycoprotein and added the CCHFV-NP (VSV-CCHFnp1 or VSV-CCHFnp2, respectively). Additionally, we prepared a vaccine candidate, VSV-CCHFgpc, in which the VSV glycoprotein was replaced with the CCHFV-GPC. Vaccine constructs induced CCHFV-specific IgG antibodies comprising largely IgG2c subclass. Only, the VSV-CCHFgpc vaccine candidate induced significant T cell immune responses directed against epitopes in the CCHFV-NSm and Gc proteins. Efficacy of the vaccine candidates was evaluated using a prime-only approach in a transiently immune-suppressed mouse model. Animals vaccinated with VSV-CCHFnp2 succumbed to lethal CCHFV challenge, while the VSV-CCHFgpc vaccine candidate afforded partial protection. In contrast, vaccination with VSV-CCHFnp1 uniformly protected animals against death. Our results demonstrate the promise of VSV-CCHFnp1 as a vaccine candidate for CCHFV and warrant continued development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"109"},"PeriodicalIF":6.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187387","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 bivalent RBD adapted COVID-19 vaccines for broad sarbecovirus immunity.","authors":"Laura A Bruno, Celeste Pueblas Castro, Agostina Demaría, Lineia Prado, Clara G Fascetto Cassero, Lucas M Saposnik, Federico Páez Córdoba, Juan Manuel Rodriguez, Giulia Piccini, Roberta Antonelli, Giulia Lapini, Nigel Temperton, Sabrina A Del Priore, Andres C Hernando Insua, Ingrid G Kaufmann, Julio C Vega, Juan M Flo, Karina A Pasquevich, Lorena M Coria, Juliana Cassataro","doi":"10.1038/s41541-025-01156-3","DOIUrl":"10.1038/s41541-025-01156-3","url":null,"abstract":"<p><p>COVID-19 vaccine adaptation is critical to respond to continuously emerging SARS-CoV-2 variants with enhanced immune evasion. The ARVAC protein subunit vaccine, based on the receptor binding domain of the spike protein of SARS-CoV-2, has been adapted to XBB.1.5 and JN.1 variants, as monovalent and bivalent formulations. Preclinical studies in mice showed that ARVAC XBB.1.5 and JN.1 monovalent vaccines induced strong neutralizing antibodies against XBB and JN.1 lineages, though with limited efficacy against phylogenetically distant variants. By contrast, bivalent formulations combining Gamma antigen with either XBB.1.5 or JN.1 antigens demonstrated superior cross-neutralizing activity, covering variants from Ancestral to JN.1. Additionally, Gamma-containing bivalent vaccines elicited neutralizing antibodies against SARS-CoV-1, highlighting their potential for broad-spectrum immunity. Cellular immune studies confirmed robust CD4⁺ T cell activation across all formulations. These findings support the continued adaptation of ARVAC to current circulant variants and propose ARVAC bivalent vaccines containing the Gamma antigen as a strategy for induction of pan-sarbecovirus immunity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"108"},"PeriodicalIF":6.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180586","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":"A VLPs based vaccine protects against Zika virus infection and prevents cerebral and testicular damage.","authors":"Nelson Côrtes, Aline Lira, Jaqueline D Q Silva, Evelyn Carvalho, Wasim A Prates-Syed, Barbara Hamaguchi, Ricardo Durães-Carvalho, Andrea Balan, Niels O S Câmara, Otavio Cabral-Marques, Norbert Pardi, Ester C Sabino, José E Krieger, Gustavo Cabral-Miranda","doi":"10.1038/s41541-025-01163-4","DOIUrl":"10.1038/s41541-025-01163-4","url":null,"abstract":"<p><p>Still, Zika virus (ZIKV) infection poses a substantial public health risk, especially for pregnant women and their fetuses, as it can result in congenital abnormalities and fetal mortality during pregnancy. Despite significant advances in understanding and combating ZIKV, considerable challenges remain in the fight against this flavivirus. A crucial component of this effort is the development of vaccines, none of which have yet been licensed for human use. Here, we present a comprehensive study of a novel ZIKV vaccine candidate based on virus-like particles (VLPs), designed to provide broad immunological protection against viral infection combined with safety, without the need for additional adjuvants. A self-adjuvanted VLPs-based vaccine displaying the envelope protein domain III (EDIII) of ZIKV was built. The EDIII protein was expressed in E. coli and chemically conjugated to QβVLPs. Immunization of C57BL/6 mice with two doses of the EDIII-QβVLPs vaccine elicited strong EDIII-specific Th1-based immune response. Notably, the vaccine induced neutralizing antibodies and conferred protection in type I IFN receptor-deficient (G129) mice against ZIKV challenge. Furthermore, vaccinated male mice were protected from ZIKV-induced cerebral and testicular damage, critical concerns for ZIKV pathogenesis. These findings suggest that the EDIII-QβVLP vaccine is a promising candidate for preventing ZIKV infection, with potential applications in combatting this and other emerging flaviviruses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"107"},"PeriodicalIF":6.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160675","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":"An antigen panel to assess the regional relevance of foot and mouth disease vaccines.","authors":"David J Paton, Ginette Wilsden, Clare Fj Browning, Efrem A Foglia, Antonello Di Nardo, Nick J Knowles, Jemma Wadsworth, Simon Gubbins, Ethel Chitsungo, Cisse Rahamatou Moustapha Boukary, Gelagay Ayelet, Charles S Bodjo, Nick Nwankpa, Emiliana Brocchi, Santina Grazioli, Anna Ludi, Donald P King","doi":"10.1038/s41541-025-01128-7","DOIUrl":"10.1038/s41541-025-01128-7","url":null,"abstract":"<p><p>Despite widespread use of inactivated vaccines to control foot-and-mouth disease (FMD), there is no systematic approach to demonstrate the regional relevance of these products against the specific serotypes and strains that circulate in endemic countries in Africa and Asia. Failure to adopt independent testing of FMD vaccines has contributed to poor trust in their quality and a lack of investment in vaccination programmes. Therefore, a reference antigen panel representing four serotypes, tailored for East Africa, has been established and used to measure FMDV-specific antibody responses in cattle after administration of FMD vaccines commercially available in the region. This revealed inconsistencies and gaps in cross-neutralisation responses that are evident for some vaccines even after giving booster doses. It is concluded that the East Africa reference antigen panel can be used to evaluate FMD vaccine potency and drive up vaccine quality. Further panels could be developed and deployed for other endemic regions.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"106"},"PeriodicalIF":6.9,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151230","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":"Comparing Moderna's mRNA-1083 and Pfizer's dual-target mRNA vaccines for influenza and COVID-19.","authors":"Adewunmi Akingbola, Abiodun Adegbesan, Kolade Adegoke, Courage Idahor, Petra Mariaria, Favour Peters, Raolat Adenike Salami, Olajide Ojo, Emmanuel Nwaeze, Owolabi Abdullahi, Joel Chuku","doi":"10.1038/s41541-025-01145-6","DOIUrl":"10.1038/s41541-025-01145-6","url":null,"abstract":"<p><p>This review examines Moderna's mRNA-1083 and Pfizer/BioNTech's mRNA-1020/1030 dual-target vaccines for COVID-19 and influenza. Both utilize mRNA technology, demonstrating strong immunogenicity and favorable safety profiles. Moderna's mRNA-1083 showed superior immune responses, while Pfizer's mRNA-1020/1030 performed well but was slightly less effective against influenza B. These vaccines simplify immunization strategies, enhance protection, and emphasize the need for global vaccine equity to prevent future outbreaks.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"105"},"PeriodicalIF":6.9,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143104","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":"Live attenuated SARS-CoV-2 vaccine OTS-228 demonstrates efficacy, safety, and stability in preclinical model.","authors":"Tobias Britzke, Nico Joël Halwe, Lorenz Ulrich, Angele Breithaupt, G Tuba Barut, Claudia Wylezich, Nadine Ebert, Bettina Salome Trüeb, Volker Thiel, Donata Hoffmann, Martin Beer, Jacob Schön","doi":"10.1038/s41541-025-01165-2","DOIUrl":"10.1038/s41541-025-01165-2","url":null,"abstract":"<p><p>Live attenuated vaccines (LAV) have the potential to meet all the criteria for an efficacious vaccine. In addition to providing protection against the target disease, they offer the potential to prevent transmission, provide cross-protection by stimulating humoral and cellular immunity, and allow versatility in application routes. The SARS-CoV-2 LAV candidate, OTS-228, has demonstrated excellent safety and high efficacy in preclinical models, inducing transmission-blocking immunity and providing full protection, even against variants such as Omicron BA.2, BA.5, and XBB.1.5. However, to ensure that OTS-228 has no dose-dependent side effects and to evaluate potential risk of reversion to virulence-a known general issue with live vaccines-detailed characterization of LAV OTS-228 is essential. To address this, we conducted four different experiments using Syrian hamsters, a model for moderate to severe COVID-19. A maximum dose trial confirmed the vaccine's full attenuation and prevention of transmission, even at high doses. In addition, four intentional serial in vivo passages demonstrated the genomic stability of the vaccine and the non-infectivity of nasal washings. Furthermore, OTS-228 maintained its attenuation and immunogenicity even after 15 additional in vitro passages, providing full protection against lung infection with virulent SARS-CoV-2 strains. Finally, a low-dose experiment confirmed the high efficacy of the vaccine candidate, establishing the protective dose 50 (PD₅₀) at less than 100 TCID₅₀ per hamster. Our results provide strong evidence for the safety and efficacy of the LAV candidate OTS-228 and supports its potential as a safe and effective vaccine in a highly relevant preclinical model.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"104"},"PeriodicalIF":6.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128376","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":"TnSeq identifies genetic requirements of Mycobacterium tuberculosis for survival under vaccine-induced immunity.","authors":"Kimra S James, Neharika Jain, Kelly Witzl, Nico Cicchetti, Sarah M Fortune, Thomas R Ioerger, Amanda J Martinot, Allison F Carey","doi":"10.1038/s41541-025-01150-9","DOIUrl":"10.1038/s41541-025-01150-9","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), remains a persistent global health challenge due to the lack of an effective vaccine. The only licensed TB vaccine, Bacille Calmette-Guerin (BCG), is a live attenuated strain of Mycobacterium bovis that protects young children from severe disease but fails to provide protection through adulthood. It is unclear why BCG provides incomplete protection despite inducing a robust Th1 immune response. We set out to interrogate mycobacterial determinants of vaccine escape using a functional genomics approach, TnSeq, to define bacterial genes required for survival in mice vaccinated with BCG, the live attenuated Mtb vaccine strain, ΔLprG, and in mice with Mtb immunity conferred by prior infection. We find that critical virulence genes associated with acute infection and exponential growth are less essential in hosts with adaptive immunity, including genes encoding the Esx-1 and Mce1 systems. Genetic requirements for Mtb growth in vaccinated and previously Mtb-infected hosts mirror the genetic requirements reported for bacteria under in vitro conditions that reflect aspects of the adaptive immune response. Across distinct immunization conditions, differences in genetic requirements between live attenuated vaccines and vaccination routes are observed, suggesting that different immunization strategies impose distinct bacterial stressors. Collectively, these data support the idea that Mtb requires genes that enable stress adaptation and growth arrest upon encountering the restrictive host environment induced by the adaptive immune response. We demonstrate that TnSeq can be used to understand the bacterial genetic requirements for survival in vaccinated hosts across pre-clinical live attenuated vaccines and therefore may be applied to other vaccine modalities. Understanding how Mtb survives vaccine-induced immunity has the potential to inform the development of new vaccines or adjuvant therapies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"103"},"PeriodicalIF":6.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127662","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":"Safety and tolerability of a novel monoclonal antibody cocktail for rabies post-exposure prophylaxis.","authors":"Nidhi Fotedar, Haradanahalli Shankaraiah Ravish","doi":"10.1038/s41541-025-01109-w","DOIUrl":"10.1038/s41541-025-01109-w","url":null,"abstract":"<p><p>Rabies is one of the most lethal viral zoonoses, particularly in low- and middle-income countries where access to post-exposure prophylaxis is limited. Conventional post-exposure prophylaxis relies on rabies immune globulin and vaccination. This study evaluated the safety of a monoclonal antibody cocktail, docaravimab and miromavimab, in 159 patients with severe animal bites. The cocktail was administered locally to 94.3 percent of participants and both locally and systemically to 5.7 percent. Adverse events were reported in 10.7 percent of cases, predominantly mild and local, with no systemic or severe reactions observed. No cases of rabies occurred during six months of follow-up. These findings suggest that the monoclonal antibody cocktail has a favorable safety profile, potentially serving as a viable alternative to traditional rabies immune globulin in post-exposure prophylaxis.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"102"},"PeriodicalIF":6.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119480","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}