Pub Date : 2024-08-27DOI: 10.1038/s41541-024-00948-3
Lin Li, Yusuke Matsui, Mary K Prahl, Arianna G Cassidy, Yarden Golan, Unurzul Jigmeddagva, Nida Ozarslan, Christine Y Lin, Sirirak Buarpung, Veronica J Gonzalez, Megan A Chidboy, Emilia Basilio, Kara L Lynch, Dongli Song, Priya Jegatheesan, Daljeet S Rai, Balaji Govindaswami, Jordan Needens, Monica Rincon, Leslie Myatt, Taha Y Taha, Mauricio Montano, Melanie Ott, Warner C Greene, Stephanie L Gaw
Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity. There was reduced anti-Omicron nAb, but the maternal-fetal transfer efficiency remained comparable to that of other variants. Vaccine-induced nAbs were transferred more efficiently than infection-induced nAbs. Anti-spike receptor binding domain (RBD) IgG was associated with nAb against wild-type (Wuhan-Hu-1) following breakthrough infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy.
针对妊娠期 SARS-CoV-2 的混合免疫尚未得到充分研究。我们对接种 mRNA 疫苗、自然感染或同时接种两种疫苗的孕妇体内的中和抗体(nAb)和结合抗体进行了全面分析。与两剂疫苗接种方案或单纯自然感染相比,第三剂疫苗可提高 nAb 水平;这种效应在混合免疫中更为明显。抗奥米克隆nAb减少,但母胎转移效率仍与其他变异株相当。疫苗诱导的 nAb 比感染诱导的 nAb 转移效率更高。突破性感染后,抗穗受体结合域(RBD)IgG与抗野生型(武汉-Hu-1)的nAb相关。疫苗接种和感染都会诱导抗 RBD IgA,这种 IgA 比抗核壳 IgA 更持久。与非妊娠对照组相比,妊娠期的 IgA 反应减弱。这些数据为妊娠期混合免疫中体液免疫反应的增强提供了更多证据。
{"title":"Neutralizing and binding antibody responses to SARS-CoV-2 with hybrid immunity in pregnancy.","authors":"Lin Li, Yusuke Matsui, Mary K Prahl, Arianna G Cassidy, Yarden Golan, Unurzul Jigmeddagva, Nida Ozarslan, Christine Y Lin, Sirirak Buarpung, Veronica J Gonzalez, Megan A Chidboy, Emilia Basilio, Kara L Lynch, Dongli Song, Priya Jegatheesan, Daljeet S Rai, Balaji Govindaswami, Jordan Needens, Monica Rincon, Leslie Myatt, Taha Y Taha, Mauricio Montano, Melanie Ott, Warner C Greene, Stephanie L Gaw","doi":"10.1038/s41541-024-00948-3","DOIUrl":"10.1038/s41541-024-00948-3","url":null,"abstract":"<p><p>Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity. There was reduced anti-Omicron nAb, but the maternal-fetal transfer efficiency remained comparable to that of other variants. Vaccine-induced nAbs were transferred more efficiently than infection-induced nAbs. Anti-spike receptor binding domain (RBD) IgG was associated with nAb against wild-type (Wuhan-Hu-1) following breakthrough infection. Both vaccination and infection-induced anti-RBD IgA, which was more durable than anti-nucleocapsid IgA. IgA response was attenuated in pregnancy compared to non-pregnant controls. These data provide additional evidence of augmentation of humoral immune responses in hybrid immunity in pregnancy.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081059","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}
Pub Date : 2024-08-21DOI: 10.1038/s41541-024-00945-6
Yu You, Ahmed M Kheimar, Tereza Vychodil, Lisa Kossak, Mohammad A Sabsabi, Andelé M Conradie, Sanjay M Reddy, Luca D Bertzbach, Benedikt B Kaufer
Marek's disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine virus is commonly used in commercial bivalent vaccines against MDV and also contains TMRs at its ends. Here, we demonstrate that SB-1 efficiently integrates its genome into the chromosomes of latently infected T cells. Deletion of the TMRs from the SB-1 genome did not affect virus replication, but severely impaired virus integration and genome maintenance in latently infected T cells and in chickens. Strikingly, the reduced integration and maintenance of latent SB-1 significantly impaired vaccine protection. Taken together, our data revealed that the TMRs facilitate SB-1 integration and that integration and/or maintenance of the latent viral genome is critical for vaccine protection.
{"title":"Telomeric repeats in the commercial SB-1 vaccine facilitate viral integration and contribute to vaccine efficacy.","authors":"Yu You, Ahmed M Kheimar, Tereza Vychodil, Lisa Kossak, Mohammad A Sabsabi, Andelé M Conradie, Sanjay M Reddy, Luca D Bertzbach, Benedikt B Kaufer","doi":"10.1038/s41541-024-00945-6","DOIUrl":"10.1038/s41541-024-00945-6","url":null,"abstract":"<p><p>Marek's disease virus (MDV) integrates its genome into the telomeres of host chromosomes and causes fatal lymphomas in chickens. This integration is facilitated by telomeric repeat sequences (TMRs) at the ends of the viral genome, and is crucial for MDV-induced lymphomagenesis. The SB-1 vaccine virus is commonly used in commercial bivalent vaccines against MDV and also contains TMRs at its ends. Here, we demonstrate that SB-1 efficiently integrates its genome into the chromosomes of latently infected T cells. Deletion of the TMRs from the SB-1 genome did not affect virus replication, but severely impaired virus integration and genome maintenance in latently infected T cells and in chickens. Strikingly, the reduced integration and maintenance of latent SB-1 significantly impaired vaccine protection. Taken together, our data revealed that the TMRs facilitate SB-1 integration and that integration and/or maintenance of the latent viral genome is critical for vaccine protection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018175","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}
Alzheimer's disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aβ-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aβ and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aβ and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aβ and pTau in 3xTg transgenic mice. It significantly eradicated Aβ plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aβ and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.
{"title":"A multi-targeting immunotherapy ameliorates multiple facets of Alzheimer's disease in 3xTg mice.","authors":"Xuejian Feng, Yunyu Hou, Jiaxin Liu, Fei Yan, Mingrui Dai, Mo Chen, Jianan Wang, Jie Li, Zhenjiang Liu, Dong Sun, Yong Zhang, Xianghui Yu, Wei Kong, Hui Wu","doi":"10.1038/s41541-024-00942-9","DOIUrl":"10.1038/s41541-024-00942-9","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an intricate disorder involving amyloid deposits, neurofibrillary tangles, and chronic neuroinflammation. Though current Aβ-directed immunotherapies effectively eliminate amyloid plaques, their limited clinical benefits and notable safety concerns arise from overlooking two other neglected neurodegenerative features. Compelling evidence highlights synergistic cooperation between Aβ and tau, underscoring the imperative need to develop combinational therapies to target the diverse pathologies of AD. In this study, we present a dual AD vaccine combining Aβ and pTau vaccines, eliciting robust and enduring antibody responses against pathological Aβ and pTau in 3xTg transgenic mice. It significantly eradicated Aβ plaques and pTau tangles, suppressed neuroinflammatory factors, and markedly enhancing cognitive abilities in 3xTg mice. Mechanistically, peripheral antibodies penetrated the brain, recognizing and inhibiting Aβ and pTau aggregation, thereby reducing their cytotoxicity. In summary, this innovative multi-targeting immunotherapy remarkably ameliorates diverse AD pathologies, demonstrating maximum benefits in slowing the clinical progression of AD.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009080","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}
Pub Date : 2024-08-19DOI: 10.1038/s41541-024-00947-4
Yuancheng Zhang, Pengfei Cui, Jianzhong Shi, Xianying Zeng, Yongping Jiang, Yuan Chen, Jie Zhang, Congcong Wang, Yan Wang, Guobin Tian, Hualan Chen, Huihui Kong, Guohua Deng
The global spread of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses threatens poultry and public health. The continuous circulation of these viruses has led to their considerable genetic and antigenic evolution, resulting in the formation of eight subclades (2.3.4.4a-h). Here, we examined the antigenic sites that determine the antigenic differences between two H5 vaccine strains, H5-Re8 (clade 2.3.4.4g) and H5-Re11 (clade 2.3.4.4h). Epitope mapping data revealed that all eight identified antigenic sites were located within two classical antigenic regions, with five sites in region A (positions 115, 120, 124, 126, and 140) and three in region B (positions 151, 156, and 185). Through antigenic cartography analysis of mutants with varying numbers of substitutions, we confirmed that a combination of mutations in these eight sites reverses the antigenicity of H5-Re11 to that of H5-Re8, and vice versa. More importantly, our analyses identified H5-Re11_Q115L/R120S/A156T (H5-Re11 + 3) as a promising candidate for a broad-spectrum vaccine, positioned centrally in the antigenic map, and offering potential universal protection against all variants within the clade 2.3.4.4. H5-Re11 + 3 serum has better cross-reactivity than sera generated with other 2.3.4.4 vaccines, and H5-Re11 + 3 vaccine provided 100% protection of chickens against antigenically drifted H5 viruses from various 2.3.4.4 antigenic groups. Our findings suggest that antigenic regions A and B are immunodominant in H5 viruses, and that antigenic cartography-guided vaccine design is a promising strategy for selecting a broad-spectrum vaccine.
H5 支系 2.3.4.4 高致病性禽流感(HPAI)病毒在全球的传播威胁着家禽和公众健康。高致病性禽流感病毒的持续传播导致其基因和抗原发生了巨大进化,形成了八个亚支系(2.3.4.4a-h)。在此,我们研究了决定两种 H5 疫苗株 H5-Re8(支系 2.3.4.4g)和 H5-Re11(支系 2.3.4.4h)之间抗原差异的抗原位点。表位图谱数据显示,所有八个确定的抗原位点都位于两个经典抗原区内,其中五个位点位于 A 区(位置 115、120、124、126 和 140),三个位点位于 B 区(位置 151、156 和 185)。通过对不同替换数量的突变体进行抗原图谱分析,我们证实这八个位点的突变组合会将 H5-Re11 的抗原性逆转为 H5-Re8 的抗原性,反之亦然。更重要的是,我们的分析发现,H5-Re11_Q115L/R120S/A156T(H5-Re11 + 3)有望成为广谱疫苗的候选品种,它位于抗原图谱的中心位置,可针对支系 2.3.4.4 中的所有变体提供潜在的普遍保护。H5-Re11 + 3血清比使用其他2.3.4.4疫苗产生的血清具有更好的交叉反应性,H5-Re11 + 3疫苗能100%地保护鸡免受来自不同2.3.4.4抗原群的抗原漂移H5病毒的感染。我们的研究结果表明,抗原区 A 和 B 是 H5 病毒的免疫优势区,以抗原图谱为指导的疫苗设计是选择广谱疫苗的一种有前途的策略。
{"title":"A broad-spectrum vaccine candidate against H5 viruses bearing different sub-clade 2.3.4.4 HA genes.","authors":"Yuancheng Zhang, Pengfei Cui, Jianzhong Shi, Xianying Zeng, Yongping Jiang, Yuan Chen, Jie Zhang, Congcong Wang, Yan Wang, Guobin Tian, Hualan Chen, Huihui Kong, Guohua Deng","doi":"10.1038/s41541-024-00947-4","DOIUrl":"10.1038/s41541-024-00947-4","url":null,"abstract":"<p><p>The global spread of H5 clade 2.3.4.4 highly pathogenic avian influenza (HPAI) viruses threatens poultry and public health. The continuous circulation of these viruses has led to their considerable genetic and antigenic evolution, resulting in the formation of eight subclades (2.3.4.4a-h). Here, we examined the antigenic sites that determine the antigenic differences between two H5 vaccine strains, H5-Re8 (clade 2.3.4.4g) and H5-Re11 (clade 2.3.4.4h). Epitope mapping data revealed that all eight identified antigenic sites were located within two classical antigenic regions, with five sites in region A (positions 115, 120, 124, 126, and 140) and three in region B (positions 151, 156, and 185). Through antigenic cartography analysis of mutants with varying numbers of substitutions, we confirmed that a combination of mutations in these eight sites reverses the antigenicity of H5-Re11 to that of H5-Re8, and vice versa. More importantly, our analyses identified H5-Re11_Q115L/R120S/A156T (H5-Re11 + 3) as a promising candidate for a broad-spectrum vaccine, positioned centrally in the antigenic map, and offering potential universal protection against all variants within the clade 2.3.4.4. H5-Re11 + 3 serum has better cross-reactivity than sera generated with other 2.3.4.4 vaccines, and H5-Re11 + 3 vaccine provided 100% protection of chickens against antigenically drifted H5 viruses from various 2.3.4.4 antigenic groups. Our findings suggest that antigenic regions A and B are immunodominant in H5 viruses, and that antigenic cartography-guided vaccine design is a promising strategy for selecting a broad-spectrum vaccine.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004889","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}
Pub Date : 2024-08-18DOI: 10.1038/s41541-024-00940-x
Eliza Kramarska, Eya Toumi, Flavia Squeglia, Diana Laverde, Valeria Napolitano, Eric Frapy, Ida Autiero, Oceane Sadones, Johannes Huebner, David Skurnik, Felipe Romero-Saavedra, Rita Berisio
ESKAPE pathogens are responsible for complicated nosocomial infections worldwide and are often resistant to commonly used antibiotics in clinical settings. Among ESKAPE, vancomycin-resistant Enterococcus faecium (VREfm) and methicillin-resistant Staphylococcus aureus (MRSA) are two important Gram-positive pathogens for which non-antibiotic alternatives are urgently needed. We previously showed that the lipoprotein AdcA of E. faecium elicits opsonic and protective antibodies against E. faecium and E. faecalis. Prompted by our observation, reported here, that AdcA also elicits opsonic antibodies against MRSA and other clinically relevant Gram-positive pathogens, we identified the dominant epitope responsible for AdcA cross-reactive activity and designed a hyper-thermostable and multi-presenting antigen, Sc(EH)3. We demonstrate that antibodies raised against Sc(EH)3 mediate opsonic killing of a wide-spectrum of Gram-positive pathogens, including VREfm and MRSA, and confer protection both in passive and active immunisation models. Our data indicate that Sc(EH)3 is a promising antigen for the development of vaccines against different Gram-positive pathogens.
{"title":"A rationally designed antigen elicits protective antibodies against multiple nosocomial Gram-positive pathogens.","authors":"Eliza Kramarska, Eya Toumi, Flavia Squeglia, Diana Laverde, Valeria Napolitano, Eric Frapy, Ida Autiero, Oceane Sadones, Johannes Huebner, David Skurnik, Felipe Romero-Saavedra, Rita Berisio","doi":"10.1038/s41541-024-00940-x","DOIUrl":"10.1038/s41541-024-00940-x","url":null,"abstract":"<p><p>ESKAPE pathogens are responsible for complicated nosocomial infections worldwide and are often resistant to commonly used antibiotics in clinical settings. Among ESKAPE, vancomycin-resistant Enterococcus faecium (VREfm) and methicillin-resistant Staphylococcus aureus (MRSA) are two important Gram-positive pathogens for which non-antibiotic alternatives are urgently needed. We previously showed that the lipoprotein AdcA of E. faecium elicits opsonic and protective antibodies against E. faecium and E. faecalis. Prompted by our observation, reported here, that AdcA also elicits opsonic antibodies against MRSA and other clinically relevant Gram-positive pathogens, we identified the dominant epitope responsible for AdcA cross-reactive activity and designed a hyper-thermostable and multi-presenting antigen, Sc(EH)<sub>3</sub>. We demonstrate that antibodies raised against Sc(EH)<sub>3</sub> mediate opsonic killing of a wide-spectrum of Gram-positive pathogens, including VREfm and MRSA, and confer protection both in passive and active immunisation models. Our data indicate that Sc(EH)<sub>3</sub> is a promising antigen for the development of vaccines against different Gram-positive pathogens.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000469","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}
Pub Date : 2024-08-17DOI: 10.1038/s41541-024-00939-4
Soo-Kyung Jeong, Su-Jin Ham, Seung-Hee Baek, Eun-Jung Jung, Hyun-Jin Jo, Hye-Ran Cha, Jae-Myun Lee, Byung Cheol Ahn, Jung Sun Yum, Eunyoung Chun
Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4+ T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001's safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.
带状疱疹(HZ)又称带状疱疹,是由潜伏的水痘-带状疱疹病毒(VZV)重新活化引起的。VZV特异性T细胞免疫反应的降低是HZ发病的重要原因。Shingrix 是一种重组带状疱疹疫苗,目前用于预防 HZ。然而,由于佐剂成分之一 QS21 的存在,Shingrix 具有较高的致反应性和注射部位疼痛。在这项研究中,我们开发了一种名为 CVI-VZV-001 的新型带状疱疹疫苗制剂,其中含有 gE 蛋白和新型脂质体佐剂 Lipo-pam™,后者由两种 TLR 激动剂组成。我们在小鼠和兔子模型中评估了 CVI-VZV-001 的免疫原性。CVI-VZV-001 引发了强有力的 gE 特异性 T 细胞免疫反应和 gE 特异性抗体生成。具体来说,CVI-VZV-001 能诱导分泌多种细胞因子的多功能 CD4+ T 细胞群。此外,CVI-VZV-001 还能在免疫后维持长达六个月的 gE 特异性免疫反应。为确保 CVI-VZV-001 的安全性,我们进行了良好实验室规范 (GLP) 毒性试验,证实 CVI-VZV-001 可以安全使用。目前,CVI-VZV-001 正在进行 I 期临床试验。这项研究表明,CVI-VZV-001 可作为 HZ 疫苗的有效候选药物,具有较高的免疫原性和安全性。
{"title":"Lipo-pam™ adjuvanted herpes zoster vaccine induces potent gE-specific cellular and humoral immune responses.","authors":"Soo-Kyung Jeong, Su-Jin Ham, Seung-Hee Baek, Eun-Jung Jung, Hyun-Jin Jo, Hye-Ran Cha, Jae-Myun Lee, Byung Cheol Ahn, Jung Sun Yum, Eunyoung Chun","doi":"10.1038/s41541-024-00939-4","DOIUrl":"10.1038/s41541-024-00939-4","url":null,"abstract":"<p><p>Herpes zoster (HZ), also known as shingles, is caused by the reactivation of latent varicella-zoster virus (VZV). Decreased VZV-specific T-cell immune responses significantly contribute to the development of HZ. Shingrix is a recombinant zoster vaccine that is currently used to prevent HZ. However, Shingrix has high reactogenicity and pain at the injection site due to QS21, one of the adjuvant components. In this study, we developed a new herpes zoster vaccine formulation called CVI-VZV-001, containing gE protein and a novel liposome-based adjuvant Lipo-pam™, which consists of two TLR agonists. We evaluated the immunogenicity of CVI-VZV-001 in mouse and rabbit models. CVI-VZV-001 elicited robust gE-specific T-cell immune responses and gE-specific antibody production. Specifically, CVI-VZV-001 induced polyfunctional CD4<sup>+</sup> T cell populations that secrete multiple cytokines. Furthermore, CVI-VZV-001 sustained the gE-specific immune responses for up to six months after immunization. To ensure CVI-VZV-001's safety for further development, we conducted a good laboratory practice (GLP) toxicity test, which confirmed that CVI-VZV-001 is safe for use. At present, CVI-VZV-001 is undergoing phase I clinical trials. This study suggests that CVI-VZV-001 can be a potent candidate for the HZ vaccine with high immunogenicity and safety.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996166","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}
Pub Date : 2024-08-17DOI: 10.1038/s41541-024-00943-8
Juan F Hernandez-Franco, Imran M Jan, Bennett D Elzey, Harm HogenEsch
A critical aspect of cancer vaccine development is the formulation with effective adjuvants. This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination. Nano-11 combined with ADU-S100 (NanoST) synergistically activated antigen-presenting cells, facilitating protein antigen cross-presentation in vitro and in vivo. Intradermal vaccination using ovalbumin (OVA) as a tumor antigen and combined with Nano-11 or NanoST prevented the development of murine B16-OVA melanoma and E.G7-OVA lymphoma tumors. The antitumor immunity was abolished by CD8+ T cell depletion but not by CD4+ T cell depletion. Therapeutic vaccination with NanoST increased mouse survival by inhibiting B16-OVA tumor growth, and this effect was further enhanced by PD-1 checkpoint blockade. Our study provides a strong rationale for developing NanoST as an adjuvant for intradermal vaccination and next-generation preventative and therapeutic cancer vaccines by STING-targeted activation.
{"title":"Intradermal vaccination with a phytoglycogen nanoparticle and STING agonist induces cytotoxic T lymphocyte-mediated antitumor immunity.","authors":"Juan F Hernandez-Franco, Imran M Jan, Bennett D Elzey, Harm HogenEsch","doi":"10.1038/s41541-024-00943-8","DOIUrl":"10.1038/s41541-024-00943-8","url":null,"abstract":"<p><p>A critical aspect of cancer vaccine development is the formulation with effective adjuvants. This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination. Nano-11 combined with ADU-S100 (NanoST) synergistically activated antigen-presenting cells, facilitating protein antigen cross-presentation in vitro and in vivo. Intradermal vaccination using ovalbumin (OVA) as a tumor antigen and combined with Nano-11 or NanoST prevented the development of murine B16-OVA melanoma and E.G7-OVA lymphoma tumors. The antitumor immunity was abolished by CD8<sup>+</sup> T cell depletion but not by CD4<sup>+</sup> T cell depletion. Therapeutic vaccination with NanoST increased mouse survival by inhibiting B16-OVA tumor growth, and this effect was further enhanced by PD-1 checkpoint blockade. Our study provides a strong rationale for developing NanoST as an adjuvant for intradermal vaccination and next-generation preventative and therapeutic cancer vaccines by STING-targeted activation.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996165","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}
Pub Date : 2024-08-14DOI: 10.1038/s41541-024-00931-y
Elif Karaaslan, Teresa E Sorvillo, Florine E M Scholte, Troy Justin O'Neal, Stephen R Welch, Katherine A Davies, JoAnn D Coleman-McCray, Jessica R Harmon, Jana M Ritter, Scott D Pegan, Joel M Montgomery, Jessica R Spengler, Christina F Spiropoulou, Éric Bergeron
Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.
{"title":"Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice.","authors":"Elif Karaaslan, Teresa E Sorvillo, Florine E M Scholte, Troy Justin O'Neal, Stephen R Welch, Katherine A Davies, JoAnn D Coleman-McCray, Jessica R Harmon, Jana M Ritter, Scott D Pegan, Joel M Montgomery, Jessica R Spengler, Christina F Spiropoulou, Éric Bergeron","doi":"10.1038/s41541-024-00931-y","DOIUrl":"10.1038/s41541-024-00931-y","url":null,"abstract":"<p><p>Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination. Vaccination with GP160, GP85, or GP38 did not confer protection, and vaccination with the MLD-associated GP38 forms blunted the humoral immune responses to GP38, worsened clinical chemistry, and increased viral RNA in the blood compared to the GP38 vaccination. In contrast, NP vaccination conferred 100% protection from lethal outcome and was associated with mild clinical disease, while the NP + GP38 combination conferred even more robust protection by reducing morbidity compared to mice receiving NP alone. Thus, recombinant CCHFV NP alone is a promising vaccine candidate conferring 100% survival against heterologous challenge. Moreover, incorporation of GP38 should be considered as it further enhances subunit vaccine efficacy by reducing morbidity in surviving animals.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982873","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}
Pub Date : 2024-08-14DOI: 10.1038/s41541-024-00934-9
Xinchun Gu, Utkarsh Agrawal, William Midgley, Stuart Bedston, Sneha N Anand, Rosalind Goudie, Rachel Byford, Mark Joy, Gavin Jamie, Uy Hoang, Jose M Ordóñez-Mena, Chris Robertson, F D Richard Hobbs, Ashley Akbari, Aziz Sheikh, Simon de Lusignan
Vaccines against COVID-19 and influenza can reduce the adverse outcomes caused by infections during pregnancy, but vaccine uptake among pregnant women has been suboptimal. We examined the COVID-19 and influenza vaccine uptake and disparities in pregnant women during the COVID-19 pandemic to inform vaccination interventions. We used data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database in England and the Secure Anonymised Information Linkage Databank in Wales. The uptake of at least one dose of vaccine was 40.2% for COVID-19 and 41.8% for influenza among eligible pregnant women. We observed disparities in COVID-19 and influenza vaccine uptake, with socioeconomically deprived and ethnic minority groups showing lower vaccination rates. The suboptimal uptake of COVID-19 and influenza vaccines, especially in those from socioeconomically deprived backgrounds and Black, mixed or other ethnic groups, underscores the necessity for interventions to reduce vaccine hesitancy and enhance acceptance in pregnant women.
{"title":"COVID-19 and influenza vaccine uptake among pregnant women in national cohorts of England and Wales.","authors":"Xinchun Gu, Utkarsh Agrawal, William Midgley, Stuart Bedston, Sneha N Anand, Rosalind Goudie, Rachel Byford, Mark Joy, Gavin Jamie, Uy Hoang, Jose M Ordóñez-Mena, Chris Robertson, F D Richard Hobbs, Ashley Akbari, Aziz Sheikh, Simon de Lusignan","doi":"10.1038/s41541-024-00934-9","DOIUrl":"10.1038/s41541-024-00934-9","url":null,"abstract":"<p><p>Vaccines against COVID-19 and influenza can reduce the adverse outcomes caused by infections during pregnancy, but vaccine uptake among pregnant women has been suboptimal. We examined the COVID-19 and influenza vaccine uptake and disparities in pregnant women during the COVID-19 pandemic to inform vaccination interventions. We used data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre database in England and the Secure Anonymised Information Linkage Databank in Wales. The uptake of at least one dose of vaccine was 40.2% for COVID-19 and 41.8% for influenza among eligible pregnant women. We observed disparities in COVID-19 and influenza vaccine uptake, with socioeconomically deprived and ethnic minority groups showing lower vaccination rates. The suboptimal uptake of COVID-19 and influenza vaccines, especially in those from socioeconomically deprived backgrounds and Black, mixed or other ethnic groups, underscores the necessity for interventions to reduce vaccine hesitancy and enhance acceptance in pregnant women.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982872","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}
Pub Date : 2024-08-13DOI: 10.1038/s41541-024-00941-w
Penelope Gray, Filipe Colaço Mariz, Carina Eklund, Tiina Eriksson, Helena Faust, Hanna Kann, Martin Müller, Jorma Paavonen, Ville N Pimenoff, Peter Sehr, Heljä-Marja Surcel, Joakim Dillner, Tim Waterboer, Matti Lehtinen
Although HPV vaccines are highly efficacious, a notable proportion of quadrivalent vaccinees are HPV18 seronegative post-vaccination. We have investigated this findings' validity by comparing vaccine-induced antibody responses using two different immunoassays. 6558 16-17-year-old females participated in the FUTURE II (NCT00092534) and PATRICIA (NCT00122681) trials in 2002-2004. Both the quadrivalent and bivalent vaccine recipients (QVR and BVR) received three doses. Twelve-year follow-up for 648 vaccinees was conducted by the Finnish Maternity Cohort. The presence of neutralising and binding HPV antibodies was analysed via HPV pseudovirion-based neutralisation and pseudovirion-binding assays. Four percent and 14.3% of the QVRs were seronegative for neutralising and binding antibodies to HPV16 and HPV18, respectively. No BVRs were HPV16/18 seronegative post-vaccination. The antibody titres were strongly correlated between the assays, Pearson's correlation coefficient, r[HPV16] = 0.92 and 0.85, and r[HPV18] = 0.91 and 0.86 among the QVRs and BVRs respectively. Fourteen percent of QVRs lacked detectable HPV18 antibodies in long-term follow-up.
{"title":"Lack of detectable HPV18 antibodies in 14% of quadrivalent vaccinees in a longitudinal cohort study.","authors":"Penelope Gray, Filipe Colaço Mariz, Carina Eklund, Tiina Eriksson, Helena Faust, Hanna Kann, Martin Müller, Jorma Paavonen, Ville N Pimenoff, Peter Sehr, Heljä-Marja Surcel, Joakim Dillner, Tim Waterboer, Matti Lehtinen","doi":"10.1038/s41541-024-00941-w","DOIUrl":"10.1038/s41541-024-00941-w","url":null,"abstract":"<p><p>Although HPV vaccines are highly efficacious, a notable proportion of quadrivalent vaccinees are HPV18 seronegative post-vaccination. We have investigated this findings' validity by comparing vaccine-induced antibody responses using two different immunoassays. 6558 16-17-year-old females participated in the FUTURE II (NCT00092534) and PATRICIA (NCT00122681) trials in 2002-2004. Both the quadrivalent and bivalent vaccine recipients (QVR and BVR) received three doses. Twelve-year follow-up for 648 vaccinees was conducted by the Finnish Maternity Cohort. The presence of neutralising and binding HPV antibodies was analysed via HPV pseudovirion-based neutralisation and pseudovirion-binding assays. Four percent and 14.3% of the QVRs were seronegative for neutralising and binding antibodies to HPV16 and HPV18, respectively. No BVRs were HPV16/18 seronegative post-vaccination. The antibody titres were strongly correlated between the assays, Pearson's correlation coefficient, r<sub>[HPV16]</sub> = 0.92 and 0.85, and r<sub>[HPV18]</sub> = 0.91 and 0.86 among the QVRs and BVRs respectively. Fourteen percent of QVRs lacked detectable HPV18 antibodies in long-term follow-up.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976256","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}