{"title":"A comprehensive investigation of Glycoprotein-based nucleic acid vaccines for Hantaan Virus.","authors":"Jiaxing Zhang, Junqi Zhang, Yanbo Wang, Yubo Sun, Yongkai Wang, Yueyue Wang, Duan Yang, Xupeng Qiao, Xiaoqian Liu, Jiaqi Ding, Xiyang Zhang, Wenbiao Zhang, Zhenjie Wang, Chenchen Hu, Chenying Han, Tianyue Liu, Shuya Yang, Yuanjie Sun, Linfeng Cheng, Dongbo Jiang, Kun Yang","doi":"10.1038/s41541-024-00991-0","DOIUrl":"https://doi.org/10.1038/s41541-024-00991-0","url":null,"abstract":"<p><p>Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, naked DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering comparable in vivo protective efficacy to the inactivated vaccines. Notably, compared to the inactivated vaccine, mRNA vaccine induced stronger virus-specific T-helper 1 cell immune response, while DNA-LNP elicited higher levels of neutralizing antibodies in mice. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"196"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504959","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 : 2024-10-23DOI: 10.1038/s41541-024-00996-9
Cong Wang, Shengnan Fu, Xin Yu, Hang Zhou, Famin Zhang, Lingling Song, Ji Zhao, Yun Yang, Jianbing Du, Qingli Luo, Jilong Shen, Li Yu
{"title":"Toxoplasma WH3 Δrop18 acts as a live attenuated vaccine against acute and chronic toxoplasmosis.","authors":"Cong Wang, Shengnan Fu, Xin Yu, Hang Zhou, Famin Zhang, Lingling Song, Ji Zhao, Yun Yang, Jianbing Du, Qingli Luo, Jilong Shen, Li Yu","doi":"10.1038/s41541-024-00996-9","DOIUrl":"https://doi.org/10.1038/s41541-024-00996-9","url":null,"abstract":"<p><p>Toxoplasma gondii is a significant zoonotic pathogen of toxoplasmosis in humans and animals. Here a live attenuated Toxoplasma vaccine of WH3 Δrop18 was developed. The results showed that all mice vaccinated with WH3 Δrop18 were able to survive when challenge with various strains of Toxoplasma, including RH (type I), ME49 (type II), WH3 or WH6 (type Chinese 1). No cysts, if few, in the brain of the vaccinated animals were seen after challenge with cyst forming strains of ME49 or WH6. Vaccination with the WH3 Δrop18 triggered a strong immune response, including significantly increased level of the cytokines (IFN-γ, IL-12, TNF-α and IL-10) and the activation of CD4<sup>+</sup> and CD8<sup>+</sup> T-lymphocytes and long term of specific antibodies against Toxoplasma. Our results strongly indicate that vaccine of WH3 Δrop18 might provide effective immune protection against a wide range strains of Toxoplasma infections and be a promising live attenuated vaccine candidate.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"197"},"PeriodicalIF":6.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504963","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":"Broad cross neutralizing antibodies against sarbecoviruses generated by SARS-CoV-2 infection and vaccination in humans.","authors":"Yabin Hu, Qian Wu, Fangfang Chang, Jing Yang, Xiaoyue Zhang, Qijie Wang, Jun Chen, Shishan Teng, Yongchen Liu, Xingyu Zheng, You Wang, Rui Lu, Dong Pan, Zhanpeng Liu, Fen Liu, Tianyi Xie, Chanfeng Wu, Yinggen Tang, Fei Tang, Jun Qian, Hongying Chen, Wenpei Liu, Yi-Ping Li, Xiaowang Qu","doi":"10.1038/s41541-024-00997-8","DOIUrl":"https://doi.org/10.1038/s41541-024-00997-8","url":null,"abstract":"<p><p>The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC<sub>50</sub>) values of 0.001-0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"195"},"PeriodicalIF":6.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504960","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":"Adenovirus type 5-expressing Gn induces better protective immunity than Gc against SFTSV infection in mice.","authors":"Hua Qian, Li Tian, Wenkai Liu, Lele Liu, Menghua Li, Zhongxin Zhao, Xiaoying Lei, Wenwen Zheng, Zhongpeng Zhao, Xuexing Zheng","doi":"10.1038/s41541-024-00993-y","DOIUrl":"10.1038/s41541-024-00993-y","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome (SFTS) is caused by the SFTS virus (SFTSV) with high morbidity and mortality. The major immunodominant region of SFTSV surface glycoprotein (G) remains unclear. In this study, we constructed adenovirus type 5 (Ad5) vectored vaccine candidates expressing different regions of SFTSV G (Gn, Gc and Gn-Gc) and evaluated their immunogenicity and protective efficacy in mice. In wild-type mice, compared with Ad5-Gc or Ad5-Gn-Gc, Ad5-Gn recruited/activated more dendritic cells and B cells in lymph nodes or peripheral blood, causing Th1-/Th2-mediated responses in splenocytes and triggered a greater level of SFTSV-neutralizing antibodies. In IFNAR Ab-treated mice, immunization of Ad5-Gn exhibited better protection against SFTSV challenge than Ad5-Gc or Ad5-Gn-Gc. Furthermore, passive immunization revealed complete protective immunity of Gn-specific serum rather than Gc. Collectively, our data demonstrated that Gn is the immunodominant fragment of SFTSV G and could be a potential candidate for SFTSV vaccine development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"194"},"PeriodicalIF":6.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471098","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 Plasmodium late liver stage arresting GAP provides superior protection in mice.","authors":"Akancha Mishra, Plabita Paul, Mrigank Srivastava, Satish Mishra","doi":"10.1038/s41541-024-00975-0","DOIUrl":"10.1038/s41541-024-00975-0","url":null,"abstract":"<p><p>Liver-stage genetically attenuated malaria parasites (GAPs) are powerful immunogens that provide protection against sporozoite challenge. We previously generated two late liver-stage-arresting GAPs by deleting the stearoyl-CoA desaturase (Scd) or sporozoite conserved orthologous transcript 1 (Scot1) genes in Plasmodium berghei. Immunization with Scd or Scot1 GAP conferred complete protection against a sporozoite challenge. In a safety study, we observed rare breakthrough blood-stage infections in mice inoculated with high doses of sporozoites, indicating that both GAPs were incompletely attenuated. In this study, we generated a Scd/Scot1 GAP by dual gene deletion. This resulted in complete attenuation of the parasites in the liver and did not transition to blood-stage infection despite a high-dose sporozoite challenge. The Scd/Scot1 KO and WT GFP parasites were indistinguishable during blood, mosquito and early liver stage development. Moreover, Scd/Scot1 KO liver-stage schizonts exhibited an abnormal apicoplast biogenesis and nuclear division phenotype, failed to form hepatic merozoites, and exhibited late liver-stage arrest. Compared with early-arresting Speld KO immunization, late-stage liver-arresting Scd/Scot1 KO induces greater and broader CD8+ T-cell responses and elicits stage-transcending immunity that provides superior protection in C57BL/6 mice. These data prove that multiple gene deletions lead to complete attenuation of the parasite and support the development of late liver stage-arresting P. falciparum GAP.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"193"},"PeriodicalIF":6.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471097","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 : 2024-10-17DOI: 10.1038/s41541-024-00967-0
Sanja Mandaric, Heather Friberg, Xavier Saez-Llorens, Charissa Borja-Tabora, Shibadas Biswal, Ian Escudero, Alice Faccin, Raphael Gottardo, Manja Brose, Nicholas Roubinis, Darlene Fladager, Rodrigo DeAntonio, Julie Anne L Dimero, Nathali Montenegro, Nicolas Folschweiller, Jeffrey R Currier, Mayuri Sharma, Vianney Tricou
{"title":"Long term T cell response and safety of a tetravalent dengue vaccine in healthy children.","authors":"Sanja Mandaric, Heather Friberg, Xavier Saez-Llorens, Charissa Borja-Tabora, Shibadas Biswal, Ian Escudero, Alice Faccin, Raphael Gottardo, Manja Brose, Nicholas Roubinis, Darlene Fladager, Rodrigo DeAntonio, Julie Anne L Dimero, Nathali Montenegro, Nicolas Folschweiller, Jeffrey R Currier, Mayuri Sharma, Vianney Tricou","doi":"10.1038/s41541-024-00967-0","DOIUrl":"https://doi.org/10.1038/s41541-024-00967-0","url":null,"abstract":"<p><p>As robust cellular responses are important for protection against dengue, this phase 2 study evaluated the kinetics and phenotype of T cell responses induced by TAK-003, a live-attenuated tetravalent dengue vaccine, in 4-16-year-old living in dengue-endemic countries (NCT02948829). Two hundred participants received TAK-003 on Days 1 and 90. Interferon-gamma (IFN-γ) enzyme-linked immunospot assay [ELISPOT] and intracellular cytokine staining were used to analyze T cell response and functionality, using peptide pools representing non-structural (NS) proteins NS3 and NS5 matching DENV-1, -2, -3, and -4 and DENV-2 NS1. One month after the second TAK-003 dose (Day 120), IFN-γ ELISPOT T cell response rates against any peptide pool were 97.1% (95% CI: 93.4% to 99.1%), and similar for baseline dengue seropositive (96.0%) and seronegative (98.6%) participants. IFN-γ ELISPOT T cell response rates at Day 120 were 79.8%, 90.2%, 77.3%, and 74.0%, against DENV-1, -2, -3, and -4, respectively, and remained elevated through 3 years post-vaccination. Multifunctional CD4 and CD8 T cell responses against DENV-2 NS peptides were observed, independent of baseline serostatus: CD8 T cells typically secreted IFN-γ and TNF-α whereas CD4 T cells secreted ≥ 2 of IFN-γ, IL-2 and TNF-α cytokines. NAb titers and seropositivity rates remained substantially elevated through 3 years post-vaccination. Overall, TAK-003 was well tolerated and elicited durable T cell responses against all four DENV serotypes irrespective of baseline serostatus in children and adolescents aged 4-16 years living in dengue-endemic countries. TAK-003-elicited CD4 and CD8 T cells were multifunctional and persisted up to 3 years post-vaccination.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"192"},"PeriodicalIF":6.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471101","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 : 2024-10-16DOI: 10.1038/s41541-024-00990-1
Michelle Galeas-Pena, Allyson Hirsch, Erin Kuang, Joseph Hoffmann, Patrick Gellings, Jasmine B Brown, Vanessa M Limbert, Claire L Callahan, James B McLachlan, Lisa A Morici
{"title":"A novel outer membrane vesicle adjuvant improves vaccine protection against Bordetella pertussis.","authors":"Michelle Galeas-Pena, Allyson Hirsch, Erin Kuang, Joseph Hoffmann, Patrick Gellings, Jasmine B Brown, Vanessa M Limbert, Claire L Callahan, James B McLachlan, Lisa A Morici","doi":"10.1038/s41541-024-00990-1","DOIUrl":"https://doi.org/10.1038/s41541-024-00990-1","url":null,"abstract":"<p><p>Pertussis is a vaccine-preventable respiratory disease caused by the Gram negative coccobacillus Bordetella pertussis. The licensed acellular pertussis (aP) vaccines protect against disease but do not prevent bacterial colonization and transmission. Here, we developed and tested an intranasal vaccine composed of aP antigens combined with T-vant, a novel adjuvant derived from bacterial outer membrane vesicles, that elicits both mucosal and systemic immune responses. We hypothesized that immunization of mice with aP-T-vant would enhance mucosal immunity and eliminate B. pertussis in the respiratory tract. In contrast to mice immunized intramuscularly with the licensed aP vaccine, intranasal immunization with aP-T-vant eliminated bacteria in both the lung and nasopharynx. Protection was associated with IFN-gamma and IL-17-producing, non-circulating CD4 + T cells in the lung and nasopharynx, and sterilizing immunity in the nasopharynx was dependent on IL-17. Novel mucosal adjuvants, such as T-vant, warrant further investigation to enhance the efficacy of next generation pertussis vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"190"},"PeriodicalIF":6.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471096","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 : 2024-10-16DOI: 10.1038/s41541-024-00981-2
Alena Reguzova, Melanie Müller, Felix Pagallies, Dominique Burri, Ferdinand Salomon, Hanns-Joachim Rziha, Zsofia Bittner-Schrader, Babs E Verstrepen, Kinga P Böszörményi, Ernst J Verschoor, Ingo Gerhauser, Knut Elbers, Meral Esen, Alessandro Manenti, Martina Monti, Hans-Georg Rammensee, Madiha Derouazi, Markus W Löffler, Ralf Amann
{"title":"A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2.","authors":"Alena Reguzova, Melanie Müller, Felix Pagallies, Dominique Burri, Ferdinand Salomon, Hanns-Joachim Rziha, Zsofia Bittner-Schrader, Babs E Verstrepen, Kinga P Böszörményi, Ernst J Verschoor, Ingo Gerhauser, Knut Elbers, Meral Esen, Alessandro Manenti, Martina Monti, Hans-Georg Rammensee, Madiha Derouazi, Markus W Löffler, Ralf Amann","doi":"10.1038/s41541-024-00981-2","DOIUrl":"https://doi.org/10.1038/s41541-024-00981-2","url":null,"abstract":"<p><p>Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N). Mono- and multiantigenic vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. Results from a SARS-CoV-2 challenge model in hamsters suggest cross-protective properties of the multiantigenic vaccine against VoC, indicating improved viral clearance with ORFV-S/N, as compared to equal doses of ORFV-S. In a nonhuman primate challenge model, vaccination with the ORFV-S/N vaccine resulted in long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of the ORFV platform for prophylactic vaccination and represent a preclinical development program supporting first-in-man studies with the multiantigenic ORFV vaccine.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"191"},"PeriodicalIF":6.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471095","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 mRNA vaccine candidate encoding H5HA clade 2.3.4.4b protects mice from clade 2.3.2.1a virus infection.","authors":"Shiho Chiba, Maki Kiso, Shinya Yamada, Kazuhiko Someya, Yoshikuni Onodera, Aya Yamaguchi, Satoko Matsunaga, Ryuta Uraki, Kiyoko Iwatsuki-Horimoto, Seiya Yamayoshi, Fumihiko Takeshita, Yoshihiro Kawaoka","doi":"10.1038/s41541-024-00988-9","DOIUrl":"https://doi.org/10.1038/s41541-024-00988-9","url":null,"abstract":"<p><p>Highly pathogenic avian influenza (HPAI) H5 viruses from different clades have been circulating globally, threatening wild/domestic birds and mammals. Given frequent spillovers and high mortality among mammals, coupled with our inability to predict which clade of H5 virus has pandemic potential, cross-clade protective HPAI H5 vaccines are urgently needed. Here, we demonstrate the applicability of a lipid nanoparticle-based mRNA vaccine modality to induce cross-protective immunity against lethal HPAI virus infection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"189"},"PeriodicalIF":6.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471100","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 : 2024-10-13DOI: 10.1038/s41541-024-00989-8
Eleni Vatzia, Basudev Paudyal, Barbara Dema, Brigid Veronica Carr, Ehsan Sedaghat-Rostami, Simon Gubbins, Bhawna Sharma, Elliot Moorhouse, Susan Morris, Marta Ulaszewska, Ronan MacLoughlin, Francisco J Salguero, Sarah C Gilbert, Elma Tchilian
{"title":"Aerosol immunization with influenza matrix, nucleoprotein, or both prevents lung disease in pig.","authors":"Eleni Vatzia, Basudev Paudyal, Barbara Dema, Brigid Veronica Carr, Ehsan Sedaghat-Rostami, Simon Gubbins, Bhawna Sharma, Elliot Moorhouse, Susan Morris, Marta Ulaszewska, Ronan MacLoughlin, Francisco J Salguero, Sarah C Gilbert, Elma Tchilian","doi":"10.1038/s41541-024-00989-8","DOIUrl":"https://doi.org/10.1038/s41541-024-00989-8","url":null,"abstract":"<p><p>Current influenza vaccines are strain-specific and require frequent updates to combat new strains, making a broadly protective influenza vaccine (BPIV) highly desirable. A promising strategy is to induce T-cell responses against internal proteins conserved across influenza strains. In this study, pH1N1 pre-exposed pigs were immunized by aerosol using viral vectored vaccines (ChAdOx2 and MVA) expressing matrix (M1) and nucleoprotein (NP). Following H3N2 challenge, all immunizations (M1, NP or NPM1) reduced lung pathology, but M1 alone offered the greatest protection. NP or NPM1 immunization induced both T-cell and antibody responses. M1 immunization generated no detectable antibodies but elicited M1-specific T-cell responses, suggesting T cell-mediated protection. Additionally, a single aerosol immunization with the ChAdOx vaccine encoding M1, NP and neuraminidase reduced lung pathology. These findings provide insights into BPIV development using a relevant large natural host, the pig.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"188"},"PeriodicalIF":6.9,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471099","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}