Pub Date : 2024-05-31DOI: 10.1038/s41541-024-00883-3
Christopher E Lopez, Zeb R Zacharias, Kathleen A Ross, Balaji Narasimhan, Thomas J Waldschmidt, Kevin L Legge
Influenza A virus (IAV) causes significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. The antigenic drift/shift of IAV continually gives rise to new strains and subtypes, aiding IAV in circumventing previously established immunity. As a result, there has been substantial interest in developing a broadly protective IAV vaccine that induces, durable immunity against multiple IAVs. Previously, a polyanhydride nanoparticle-based vaccine or nanovaccine (IAV-nanovax) encapsulating H1N1 IAV antigens was reported, which induced pulmonary B and T cell immunity and resulted in cross-strain protection against IAV. A key feature of IAV-nanovax is its ability to easily incorporate diverse proteins/payloads, potentially increasing its ability to provide broad protection against IAV and/or other pathogens. Due to human susceptibility to both H1N1 and H3N2 IAV, several H3N2 nanovaccines were formulated herein with multiple IAV antigens to examine the "plug-and-play" nature of the polyanhydride nanovaccine platform and determine their ability to induce humoral and cellular immunity and broad-based protection similar to IAV-nanovax. The H3N2-based IAV nanovaccine formulations induced systemic and mucosal B cell responses which were associated with antigen-specific antibodies. Additionally, systemic and lung-tissue resident CD4 and CD8 T cell responses were enhanced post-vaccination. These immune responses corresponded with protection against both homologous and heterosubtypic IAV infection. Overall, these results demonstrate the plug-and-play nature of the polyanhydride nanovaccine platform and its ability to generate immunity and protection against IAV utilizing diverse antigenic payloads.
{"title":"Polyanhydride nanovaccine against H3N2 influenza A virus generates mucosal resident and systemic immunity promoting protection.","authors":"Christopher E Lopez, Zeb R Zacharias, Kathleen A Ross, Balaji Narasimhan, Thomas J Waldschmidt, Kevin L Legge","doi":"10.1038/s41541-024-00883-3","DOIUrl":"10.1038/s41541-024-00883-3","url":null,"abstract":"<p><p>Influenza A virus (IAV) causes significant morbidity and mortality worldwide due to seasonal epidemics and periodic pandemics. The antigenic drift/shift of IAV continually gives rise to new strains and subtypes, aiding IAV in circumventing previously established immunity. As a result, there has been substantial interest in developing a broadly protective IAV vaccine that induces, durable immunity against multiple IAVs. Previously, a polyanhydride nanoparticle-based vaccine or nanovaccine (IAV-nanovax) encapsulating H1N1 IAV antigens was reported, which induced pulmonary B and T cell immunity and resulted in cross-strain protection against IAV. A key feature of IAV-nanovax is its ability to easily incorporate diverse proteins/payloads, potentially increasing its ability to provide broad protection against IAV and/or other pathogens. Due to human susceptibility to both H1N1 and H3N2 IAV, several H3N2 nanovaccines were formulated herein with multiple IAV antigens to examine the \"plug-and-play\" nature of the polyanhydride nanovaccine platform and determine their ability to induce humoral and cellular immunity and broad-based protection similar to IAV-nanovax. The H3N2-based IAV nanovaccine formulations induced systemic and mucosal B cell responses which were associated with antigen-specific antibodies. Additionally, systemic and lung-tissue resident CD4 and CD8 T cell responses were enhanced post-vaccination. These immune responses corresponded with protection against both homologous and heterosubtypic IAV infection. Overall, these results demonstrate the plug-and-play nature of the polyanhydride nanovaccine platform and its ability to generate immunity and protection against IAV utilizing diverse antigenic payloads.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183516","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 : 2024-05-29DOI: 10.1038/s41541-024-00884-2
Katherine B Carlson, Anne Dilley, Thomas O'Grady, Jordan A Johnson, Ben Lopman, Emma Viscidi
Norovirus is a leading cause of acute gastroenteritis (AGE) globally. AGE resulting from norovirus causes significant morbidity and mortality in countries of all income levels, particularly among young children and older adults. Prevention of norovirus AGE represents a unique challenge as the virus is genetically diverse with multiple genogroups and genotypes cocirculating globally and causing disease in humans. Variants of the GII.4 genotype are typically the most common genotype, and other genotypes cause varying amounts of disease year-to-year, with GII.2, GII.3, and GII.6 most prevalent in recent years. Noroviruses are primarily transmitted via the fecal-oral route and only a very small number of virions are required for infection, which makes outbreaks of norovirus extremely difficult to control when they occur. Settings like long-term care facilities, daycares, and hospitals are at high risk of outbreaks and can have very high attack rates resulting in substantial costs and disease burden. Severe cases of norovirus AGE are most common in vulnerable patient populations, such as infants, the elderly, and immunocompromised individuals, with available treatments limited to rehydration therapies and supportive care. To date, there are no FDA-approved norovirus vaccines; however, several candidates are currently in development. Given the substantial human and economic burden associated with norovirus AGE, a vaccine to prevent morbidity and mortality and protect vulnerable populations could have a significant impact on global public health.
诺如病毒是全球急性肠胃炎(AGE)的主要病因。在所有收入水平的国家,诺如病毒导致的急性肠胃炎都会造成严重的发病率和死亡率,尤其是幼儿和老年人。预防诺如病毒 AGE 是一项独特的挑战,因为该病毒的基因多样,有多个基因组和基因型在全球范围内共同流行并导致人类发病。GII.4 基因型的变种通常是最常见的基因型,其他基因型每年导致的疾病数量各不相同,其中 GII.2、GII.3 和 GII.6 近年来最为流行。诺如病毒主要通过粪-口途径传播,感染时只需要极少量的病毒,因此诺如病毒爆发时极难控制。长期护理机构、托儿所和医院等场所是诺如病毒爆发的高危场所,其发病率极高,造成巨大的成本和疾病负担。诺如病毒 AGE 的严重病例最常见于婴儿、老年人和免疫力低下者等易感人群,现有的治疗方法仅限于补液疗法和支持性护理。迄今为止,美国食品及药物管理局尚未批准诺如病毒疫苗,但目前有几种候选疫苗正在研发中。鉴于诺如病毒 AGE 对人类和经济造成的巨大负担,预防发病和死亡并保护易感人群的疫苗将对全球公共卫生产生重大影响。
{"title":"A narrative review of norovirus epidemiology, biology, and challenges to vaccine development.","authors":"Katherine B Carlson, Anne Dilley, Thomas O'Grady, Jordan A Johnson, Ben Lopman, Emma Viscidi","doi":"10.1038/s41541-024-00884-2","DOIUrl":"10.1038/s41541-024-00884-2","url":null,"abstract":"<p><p>Norovirus is a leading cause of acute gastroenteritis (AGE) globally. AGE resulting from norovirus causes significant morbidity and mortality in countries of all income levels, particularly among young children and older adults. Prevention of norovirus AGE represents a unique challenge as the virus is genetically diverse with multiple genogroups and genotypes cocirculating globally and causing disease in humans. Variants of the GII.4 genotype are typically the most common genotype, and other genotypes cause varying amounts of disease year-to-year, with GII.2, GII.3, and GII.6 most prevalent in recent years. Noroviruses are primarily transmitted via the fecal-oral route and only a very small number of virions are required for infection, which makes outbreaks of norovirus extremely difficult to control when they occur. Settings like long-term care facilities, daycares, and hospitals are at high risk of outbreaks and can have very high attack rates resulting in substantial costs and disease burden. Severe cases of norovirus AGE are most common in vulnerable patient populations, such as infants, the elderly, and immunocompromised individuals, with available treatments limited to rehydration therapies and supportive care. To date, there are no FDA-approved norovirus vaccines; however, several candidates are currently in development. Given the substantial human and economic burden associated with norovirus AGE, a vaccine to prevent morbidity and mortality and protect vulnerable populations could have a significant impact on global public health.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175725","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 : 2024-05-28DOI: 10.1038/s41541-024-00886-0
Muriel Aguilar-Bretones, Yvette den Hartog, Laura L A van Dijk, S Reshwan K Malahe, Marjolein Dieterich, Héctor Tejeda Mora, Yvonne M Mueller, Marion P G Koopmans, Marlies E J Reinders, Carla C Baan, Gijsbert P van Nierop, Rory D de Vries
Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.
由于在首次接种疫苗之前感染过 SARS-CoV-2 而获得混合免疫力的健康人与只接种疫苗的人相比,具有更强的免疫反应。然而,人们对具有混合免疫力的肾病患者的抗体、B 细胞和 T 细胞反应的特点知之甚少。在此,我们探讨了无症状或轻度冠状病毒病-2019(COVID-19)后具有混合免疫力的肾病患者与对照组之间的差异。我们研究了慢性肾病或透析患者、肾移植受者和具有混合免疫力的对照组对初次接种 mRNA-1273 疫苗的 SARS-CoV-2 特异性免疫反应的动力学、幅度、广度和表型。虽然单独接种疫苗对肾病患者的免疫原性较低,但 mRNA-1273 能诱导曾感染过 SARS-CoV-2 的患者产生强有力的免疫反应。相反,具有混合免疫力的肾病患者产生的 SARS-CoV-2 抗体、B 细胞和 T 细胞反应与对照组相同或更强。表型分析表明,各组的尖峰(S)特异性 B 细胞在淋巴结归巢和记忆表型上存在差异,但各组的 S 特异性 T 细胞反应在表型上是一致的。混合免疫肾病患者免疫反应的异质性需要在更大的群体中进行进一步研究,以揭示长期保护的标志物,从而用于设计有针对性的疫苗方案。
{"title":"SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity.","authors":"Muriel Aguilar-Bretones, Yvette den Hartog, Laura L A van Dijk, S Reshwan K Malahe, Marjolein Dieterich, Héctor Tejeda Mora, Yvonne M Mueller, Marion P G Koopmans, Marlies E J Reinders, Carla C Baan, Gijsbert P van Nierop, Rory D de Vries","doi":"10.1038/s41541-024-00886-0","DOIUrl":"10.1038/s41541-024-00886-0","url":null,"abstract":"<p><p>Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161978","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 : 2024-05-25DOI: 10.1038/s41541-024-00875-3
Leda Lotspeich-Cole, Swetha Parvathaneni, Jiro Sakai, Lunhua Liu, Kazuyo Takeda, Robert C. Lee, M. Akkoyunlu
{"title":"Sustained antigen delivery improves germinal center reaction and increases antibody responses in neonatal mice","authors":"Leda Lotspeich-Cole, Swetha Parvathaneni, Jiro Sakai, Lunhua Liu, Kazuyo Takeda, Robert C. Lee, M. Akkoyunlu","doi":"10.1038/s41541-024-00875-3","DOIUrl":"https://doi.org/10.1038/s41541-024-00875-3","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1038/s41541-024-00889-x
Sara E Woodson, Kaitlyn M Morabito
{"title":"Continuing development of vaccines and monoclonal antibodies against Zika virus.","authors":"Sara E Woodson, Kaitlyn M Morabito","doi":"10.1038/s41541-024-00889-x","DOIUrl":"10.1038/s41541-024-00889-x","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11126562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094055","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 : 2024-05-23DOI: 10.1038/s41541-024-00877-1
Teresa E Sorvillo, Elif Karaaslan, Florine E M Scholte, Stephen R Welch, JoAnn D Coleman-McCray, Sarah C Genzer, Jana M Ritter, Heather M Hayes, Shilpi Jain, Scott D Pegan, Éric Bergeron, Joel M Montgomery, Christina F Spiropoulou, Jessica R Spengler
Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar-/- mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar-/- mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.
{"title":"Replicon particle vaccination induces non-neutralizing anti-nucleoprotein antibody-mediated control of Crimean-Congo hemorrhagic fever virus.","authors":"Teresa E Sorvillo, Elif Karaaslan, Florine E M Scholte, Stephen R Welch, JoAnn D Coleman-McCray, Sarah C Genzer, Jana M Ritter, Heather M Hayes, Shilpi Jain, Scott D Pegan, Éric Bergeron, Joel M Montgomery, Christina F Spiropoulou, Jessica R Spengler","doi":"10.1038/s41541-024-00877-1","DOIUrl":"10.1038/s41541-024-00877-1","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe human disease and is considered a WHO priority pathogen due to the lack of efficacious vaccines and antivirals. A CCHF virus replicon particle (VRP) has previously shown protective efficacy in a lethal Ifnar<sup>-/-</sup> mouse model when administered as a single dose at least 3 days prior to challenge. Here, we determine that non-specific immune responses are not sufficient to confer short-term protection, since Lassa virus VRP vaccination 3 days prior to CCHFV challenge was not protective. We also investigate how CCHF VRP vaccination confers protective efficacy by examining viral kinetics, histopathology, clinical analytes and immunity early after challenge (3 and 6 days post infection) and compare to unvaccinated controls. We characterize how these effects differ based on vaccination period and correspond to previously reported CCHF VRP-mediated protection. Vaccinating Ifnar<sup>-/-</sup> mice with CCHF VRP 28, 14, 7, or 3 days prior to challenge, all known to confer complete protection, significantly reduced CCHFV viral load, mucosal shedding, and markers of clinical disease, with greater reductions associated with longer vaccination periods. Interestingly, there were no significant differences in innate immune responses, T cell activation, or antibody titers after challenge between groups of mice vaccinated a week or more before challenge, but higher anti-NP antibody avidity and effector function (ADCD) were positively associated with longer vaccination periods. These findings support the importance of antibody-mediated responses in VRP vaccine-mediated protection against CCHFV infection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088004","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 : 2024-05-23DOI: 10.1038/s41541-024-00870-8
Bryce M Warner, Jacob G E Yates, Robert Vendramelli, Thang Truong, Courtney Meilleur, Lily Chan, Alexander Leacy, Phuc H Pham, Yanlong Pei, Leonardo Susta, Sarah K Wootton, Darwyn Kobasa
The rapid development and deployment of vaccines following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions of lives. Despite their immense success, there remains a need for next-generation vaccination approaches for SARS-CoV-2 and future emerging coronaviruses and other respiratory viruses. Here we utilized a Newcastle Disease virus (NDV) vectored vaccine expressing the ancestral SARS-CoV-2 spike protein in a pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters and K18 mice against Delta and Omicron SARS-CoV-2 variants of concern. Additionally, intranasal vaccination induced robust, durable protection that was extended to 6 months post-vaccination. Overall, our data provide evidence that NDV-vectored vaccines represent a viable next-generation mucosal vaccination approach.
{"title":"Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges.","authors":"Bryce M Warner, Jacob G E Yates, Robert Vendramelli, Thang Truong, Courtney Meilleur, Lily Chan, Alexander Leacy, Phuc H Pham, Yanlong Pei, Leonardo Susta, Sarah K Wootton, Darwyn Kobasa","doi":"10.1038/s41541-024-00870-8","DOIUrl":"10.1038/s41541-024-00870-8","url":null,"abstract":"<p><p>The rapid development and deployment of vaccines following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions of lives. Despite their immense success, there remains a need for next-generation vaccination approaches for SARS-CoV-2 and future emerging coronaviruses and other respiratory viruses. Here we utilized a Newcastle Disease virus (NDV) vectored vaccine expressing the ancestral SARS-CoV-2 spike protein in a pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters and K18 mice against Delta and Omicron SARS-CoV-2 variants of concern. Additionally, intranasal vaccination induced robust, durable protection that was extended to 6 months post-vaccination. Overall, our data provide evidence that NDV-vectored vaccines represent a viable next-generation mucosal vaccination approach.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087932","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 : 2024-05-23DOI: 10.1038/s41541-024-00876-2
Boris Julg, Kathryn E Stephenson, Frank Tomaka, Stephen R Walsh, C Sabrina Tan, Ludo Lavreys, Michal Sarnecki, Jessica L Ansel, Diane G Kanjilal, Kate Jaegle, Tessa Speidel, Joseph P Nkolola, Erica N Borducchi, Esmee Braams, Laura Pattacini, Eleanor Burgess, Shlomi Ilan, Yannic Bartsch, Katherine E Yanosick, Michael S Seaman, Daniel J Stieh, Janine van Duijn, Wouter Willems, Merlin L Robb, Nelson L Michael, Bruce D Walker, Maria Grazia Pau, Hanneke Schuitemaker, Dan H Barouch
Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.
{"title":"Immunogenicity of 2 therapeutic mosaic HIV-1 vaccine strategies in individuals with HIV-1 on antiretroviral therapy.","authors":"Boris Julg, Kathryn E Stephenson, Frank Tomaka, Stephen R Walsh, C Sabrina Tan, Ludo Lavreys, Michal Sarnecki, Jessica L Ansel, Diane G Kanjilal, Kate Jaegle, Tessa Speidel, Joseph P Nkolola, Erica N Borducchi, Esmee Braams, Laura Pattacini, Eleanor Burgess, Shlomi Ilan, Yannic Bartsch, Katherine E Yanosick, Michael S Seaman, Daniel J Stieh, Janine van Duijn, Wouter Willems, Merlin L Robb, Nelson L Michael, Bruce D Walker, Maria Grazia Pau, Hanneke Schuitemaker, Dan H Barouch","doi":"10.1038/s41541-024-00876-2","DOIUrl":"10.1038/s41541-024-00876-2","url":null,"abstract":"<p><p>Mosaic HIV-1 vaccines have been shown to elicit robust humoral and cellular immune responses in people living with HIV-1 (PLWH), that had started antiretroviral therapy (ART) during acute infection. We evaluated the safety and immunogenicity of 2 mosaic vaccine regimens in virologically suppressed individuals that had initiated ART during the chronic phase of infection, exemplifying the majority of PLWH. In this double-blind, placebo-controlled phase 1 trial (IPCAVD013/HTX1002) 25 ART-suppressed PLWH were randomized to receive Ad26.Mos4.HIV/MVA-Mosaic (Ad26/MVA) (n = 10) or Ad26.Mos4.HIV/Ad26.Mos4.HIV plus adjuvanted gp140 protein (Ad26/Ad26+gp140) (n = 9) or placebo (n = 6). Primary endpoints included safety and tolerability and secondary endpoints included HIV-specific binding and neutralizing antibody titers and HIV-specific T cell responses. Both vaccine regimens were well tolerated with pain/tenderness at the injection site and fatigue, myalgia/chills and headache as the most commonly reported solicited local and grade 3 systemic adverse events, respectively. In the Ad26/Ad26+gp140 group, Env-specific IFN-γ T cell responses showed a median 12-fold increase while responses to Gag and Pol increased 1.8 and 2.4-fold, respectively. The breadth of T cell responses to individual peptide subpools increased from 11.0 pre-vaccination to 26.0 in the Ad26/Ad26+gp140 group and from 10.0 to 14.5 in the Ad26/MVA group. Ad26/Ad26+gp140 vaccination increased binding antibody titers against vaccine-matched clade C Env 5.5-fold as well as augmented neutralizing antibody titers against Clade C pseudovirus by 7.2-fold. Both vaccine regimens were immunogenic, while the addition of the protein boost resulted in additional T cell and augmented binding and neutralizing antibody titers. These data suggest that the Ad26/Ad26+gp140 regimen should be tested further.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087927","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 : 2024-05-22DOI: 10.1038/s41541-024-00878-0
Emma S Chambers, Weigang Cai, Giulia Vivaldi, David A Jolliffe, Natalia Perdek, Wenhao Li, Sian E Faustini, Joseph M Gibbons, Corinna Pade, Alex G Richter, Anna K Coussens, Adrian R Martineau
Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.
{"title":"Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.","authors":"Emma S Chambers, Weigang Cai, Giulia Vivaldi, David A Jolliffe, Natalia Perdek, Wenhao Li, Sian E Faustini, Joseph M Gibbons, Corinna Pade, Alex G Richter, Anna K Coussens, Adrian R Martineau","doi":"10.1038/s41541-024-00878-0","DOIUrl":"10.1038/s41541-024-00878-0","url":null,"abstract":"<p><p>Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082012","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 : 2024-05-20DOI: 10.1038/s41541-024-00887-z
David W Hawman, Shanna S Leventhal, Kimberly Meade-White, Amit Khandhar, Justin Murray, Jamie Lovaglio, Carl Shaia, Greg Saturday, Troy Hinkley, Jesse Erasmus, Heinz Feldmann
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with a wide geographic distribution. In recent years the geographic range of Crimean-Congo hemorrhagic fever virus (CCHFV) and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently, there are no widely available vaccines, and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Here we evaluate a promising replicating RNA vaccine in a rhesus macaque (Macaca mulatta) model of CCHF. This model provides an alternative to the established cynomolgus macaque model and recapitulates mild-to-moderate human disease. Rhesus macaques infected with CCHFV consistently exhibit viremia, detectable viral RNA in a multitude of tissues, and moderate pathology in the liver and spleen. We used this model to evaluate the immunogenicity and protective efficacy of a replicating RNA vaccine. Rhesus macaques vaccinated with RNAs expressing the CCHFV nucleoprotein and glycoprotein precursor developed robust non-neutralizing humoral immunity against the CCHFV nucleoprotein and had significant protection against the CCHFV challenge. Together, our data report a model of CCHF using rhesus macaques and demonstrate that our replicating RNA vaccine is immunogenic and protective in non-human primates after a prime-boost immunization.
{"title":"A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever.","authors":"David W Hawman, Shanna S Leventhal, Kimberly Meade-White, Amit Khandhar, Justin Murray, Jamie Lovaglio, Carl Shaia, Greg Saturday, Troy Hinkley, Jesse Erasmus, Heinz Feldmann","doi":"10.1038/s41541-024-00887-z","DOIUrl":"10.1038/s41541-024-00887-z","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne febrile illness with a wide geographic distribution. In recent years the geographic range of Crimean-Congo hemorrhagic fever virus (CCHFV) and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently, there are no widely available vaccines, and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Here we evaluate a promising replicating RNA vaccine in a rhesus macaque (Macaca mulatta) model of CCHF. This model provides an alternative to the established cynomolgus macaque model and recapitulates mild-to-moderate human disease. Rhesus macaques infected with CCHFV consistently exhibit viremia, detectable viral RNA in a multitude of tissues, and moderate pathology in the liver and spleen. We used this model to evaluate the immunogenicity and protective efficacy of a replicating RNA vaccine. Rhesus macaques vaccinated with RNAs expressing the CCHFV nucleoprotein and glycoprotein precursor developed robust non-neutralizing humoral immunity against the CCHFV nucleoprotein and had significant protection against the CCHFV challenge. Together, our data report a model of CCHF using rhesus macaques and demonstrate that our replicating RNA vaccine is immunogenic and protective in non-human primates after a prime-boost immunization.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11106275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071510","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}