{"title":"Optimization of the preparation method of inactivated intact virus particle vaccine for COVID-19","authors":"Marumi Ohno , Toshiki Sekiya , Richard Obeng-Kyeremeh , Chimuka Handabile , Minori Haruta , Naoki Nomura , Tomomi Kawakita , Masashi Shingai , Hiroshi Kida","doi":"10.1016/j.vaccine.2025.127173","DOIUrl":"10.1016/j.vaccine.2025.127173","url":null,"abstract":"<div><div>It has been recognized that it is difficult to maintain the virus particle structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may be associated with lower immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID-19). We have previously demonstrated that an intact structure of the virus particles is critical for influenza inactivated whole virus particle vaccine (WPV) to be immunogenically potent. Here, we tested 37, 35, 33, and 31 °C for the virus propagation temperatures and the timing of formaldehyde treatment of the virus before and after centrifugation-based purification to obtain virus particles with an intact structure. Virus particles cultured at 33 °C retained spike proteins on the surface the most abundantly. The pretreatment of the virus with formaldehyde prevented the dissociation of the spike proteins from the viral surface during the centrifugation-based purification. The immunogenicity of the prepared vaccines, intact WPV and non-intact WPV that had lost the spike proteins, was evaluated in a mouse model. A single dose of intact WPV effectively induced humoral immunity compared to non-intact WPV, as indicated by higher titers of neutralizing antibodies. After a virus challenge, the mice vaccinated with a single dose of inactivated intact WPV showed less severe weight loss and lower virus titers in the lungs compared to those vaccinated with non-intact WPV. These results demonstrate the importance of the structural integrity of WPV in inducing effective and protective immunity, and provide significant insight into the development of COVID-19 WPV for practical use.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127173"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-24DOI: 10.1016/j.vaccine.2025.127141
Hannah Melchinger , Maya Khemsara , Noureen Ahmed , Sameer M. Belgaumi , Krutika Kuppalli , Saad B. Omer , Amyn A. Malik
{"title":"Assessment of mpox awareness, attitudes, and vaccination intent among the United States public following an outbreak of mpox clade Ib in Africa.","authors":"Hannah Melchinger , Maya Khemsara , Noureen Ahmed , Sameer M. Belgaumi , Krutika Kuppalli , Saad B. Omer , Amyn A. Malik","doi":"10.1016/j.vaccine.2025.127141","DOIUrl":"10.1016/j.vaccine.2025.127141","url":null,"abstract":"<div><div>During the global outbreak of Clade IIb mpox (formerly known as monkeypox) in 2022, a survey of the US adult population (18+) found that knowledge of mpox and intention to vaccinate against it were low. Given the ongoing surge of Clade Ib in Africa, and recent reports of cases outside of Africa and in the US, we conducted a similar survey to assess whether US adult knowledge, attitudes, and practices towards mpox have changed since 2022. The survey, hosted by online survey company CloudResearch, asked questions about mpox awareness, risk perception, intention to vaccinate, and trusted sources of information. We found that 58% (95% CI 52–62) of US adults would be willing to receive the mpox vaccine if recommended by their doctor or health authority, a 12% increase from our 2022 results. Respondents from Health and Humans Services (HHS) Region 1 (CT, ME, MA, NH, RI, VT) were least likely to receive the vaccine, even if recommended to do so. Self-reported knowledge of mpox (40%), as well as perceived self-efficacy (55%) and mean risk perception (3.2) have also increased since the 2022 survey. Healthcare professionals remain the most trusted source of information (73%), and trust in the US government to provide accurate information has increased (58%). These results highlight the need for ongoing education among US adults to improve awarness of and vaccination intention for the mpox vaccine. The consistently high degrees of trust placed in healthcare professionals and officials should guide future communications about mpox and other infectious diseases, and reinforce the importance of leveraging trusted sources to share essential public health information.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127141"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-24DOI: 10.1016/j.vaccine.2025.127160
Quisha Bustamante , Dominic Sparkes , Lucy Findlater , Katie Munro , Irina Lut , Jameel Khawam , Sophie Russell , Ana Atti , Sarah Foulkes , Susan Hopkins , Victoria Hall , Jasmin Islam
{"title":"Understanding occupational and attitudinal factors influencing UK healthcare worker decisions for COVID-19 and influenza vaccination: A cross-sectional survey within SIREN","authors":"Quisha Bustamante , Dominic Sparkes , Lucy Findlater , Katie Munro , Irina Lut , Jameel Khawam , Sophie Russell , Ana Atti , Sarah Foulkes , Susan Hopkins , Victoria Hall , Jasmin Islam","doi":"10.1016/j.vaccine.2025.127160","DOIUrl":"10.1016/j.vaccine.2025.127160","url":null,"abstract":"<div><h3>Background</h3><div>Seasonal vaccination of healthcare workers (HCWs) against COVID-19 and influenza has been recommended to protect patients and the workforce against Winter pressures. We aimed to investigate demographic, occupational, accessibility and tolerability factors associated with COVID-19 and influenza vaccination among HCWs within the SIREN study cohort in 2023/24.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional survey between 29 February-22 March 2024 within SIREN, a prospective HCW cohort across the UK. Adjusted odds ratios (aOR) and 95 % confidence intervals (CI) from a multivariable regression analysis were used to identify factors associated with vaccination. Proportions were calculated to describe the rationale for receiving/not receiving seasonal vaccines.</div></div><div><h3>Results</h3><div>A total of 5357/33,007 (16.2 %) SIREN participants completed the survey. 66.7 % (3572/5357) received both vaccines, 2.4 % (129/5357) COVID-19 only, 12.4 % (662/5357) influenza only, and 18.3 % (979/5357) neither. Participants were more likely to receive any vaccine if they were over 65 years (aOR 2.73, 95 % CI: 1.64–4.55), a doctor (aOR 2.28, 95 % CI: 1.70–3.05) or had a chronic respiratory condition (aOR 1.52, 95 % CI: 1.20–1.92). Participants of Black ethnicity were less likely to be vaccinated (aOR 0.42, 95 % CI: 0.27–0.66). The top reason for vaccination was to protect oneself (81.6 %). Concern about long-term side effects was the main reason for not getting vaccinated among those who did not receive the COVID-19 vaccine (30.1 %).</div></div><div><h3>Discussion</h3><div>We observed differences in uptake and attitudes towards seasonal vaccines among UK HCWs within the SIREN cohort. Differences in demographic characteristics, occupation and attitudes varied by vaccine type and this should be considered when planning seasonal vaccination programmes to protect the health workforce.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127160"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-24DOI: 10.1016/j.vaccine.2025.127154
Jacob Jacovetty , Abram L. Wagner , Ichsan Ichsan , Amanda Yufika , Tita Menawati , Rosaria Indah , Fitdha Kairadini , Antonios M. Koumpias , Harapan Harapan
{"title":"Associations between parental vaccine hesitancy, religion-based vaccine hesitancy, and childhood full vaccination in a cross-sectional study in Aceh, Indonesia, 2023","authors":"Jacob Jacovetty , Abram L. Wagner , Ichsan Ichsan , Amanda Yufika , Tita Menawati , Rosaria Indah , Fitdha Kairadini , Antonios M. Koumpias , Harapan Harapan","doi":"10.1016/j.vaccine.2025.127154","DOIUrl":"10.1016/j.vaccine.2025.127154","url":null,"abstract":"<div><h3>Background</h3><div>Many Muslims in Indonesia have religion-based concerns surrounding vaccine ingredients. The aim of this study was to examine the correlation between parental religion-based vaccine hesitancy and other types of vaccine hesitancy, and to assess the association between parental vaccine hesitancy, religion-based vaccine hesitancy, and childhood full vaccination.</div></div><div><h3>Methods</h3><div>This study was based on a multistage, cluster sample within in Aceh, Indonesia. The survey included demographic characteristics, measures of vaccine hesitancy, structural barriers, and vaccination status questions. We examined correlations using Pearson correlation coefficient and the relationship between vaccine hesitancy, and religion-based vaccine concerns, on a child being fully vaccinated using a Poisson regression model with robust variance estimation.</div></div><div><h3>Results</h3><div>The study included 1689 participants and all were Muslim. Only 34 % of children were fully vaccinated, 29 % of parents were vaccine hesitant, and 32 % expressed concerns that vaccine ingredients were not halal. Childhood vaccination status, vaccine hesitancy, and religion-based concerns were all significantly correlated with each other. In a multivariable model, vaccine hesitancy and religion-based concerns were both directly significant in their relationship with childhood vaccination status. Those who were vaccine hesitant were only 0.21 times as likely to have a child fully vaccinated compared to those not hesitant (95 % CI: 0.16, 0.37). Those with concerns about vaccine ingredients being halal also were less likely to have a child fully vaccinated (PR: 0.55, 95 % CI: 0.42, 0.72).</div></div><div><h3>Conclusion</h3><div>We found that religious-based vaccine concerns were highly prominent in this population, and likely a large contributor to vaccine hesitancy. Efforts to improve vaccination coverage should focus on addressing religious concerns and working closely with religious leaders to build trust and disseminate accurate information about vaccines.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127154"},"PeriodicalIF":4.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-23DOI: 10.1016/j.vaccine.2025.127120
Leah J. McGrath , Farid L. Khan , Santiago M.C. Lopez , Matthew A. Brouillette , Kathleen M. Andersen , Tiange Yu , Benjamin T. Carter , Laura A. Puzniak , John M. McLaughlin
{"title":"2023–2024 COVID-19 vaccine uptake among immunocompromised individuals in two US states","authors":"Leah J. McGrath , Farid L. Khan , Santiago M.C. Lopez , Matthew A. Brouillette , Kathleen M. Andersen , Tiange Yu , Benjamin T. Carter , Laura A. Puzniak , John M. McLaughlin","doi":"10.1016/j.vaccine.2025.127120","DOIUrl":"10.1016/j.vaccine.2025.127120","url":null,"abstract":"<div><h3>Background</h3><div>Uptake of COVID-19 vaccines has declined over time, however, little data exist describing uptake among the immunocompromised who remain at high risk of severe disease. We evaluated XBB COVID-19 vaccine uptake during the 2023–2024 season among immunocompromised persons who had previously received a COVID-19 vaccine in two large, diverse US states.</div></div><div><h3>Methods</h3><div>Using data from state vaccine registries linked to insurance claims, we conducted a retrospective cohort study among individuals ≥6 months of age living in California or Louisiana as of September 11, 2023 who (1) had continuous pharmacy and medical enrollment in an insurance plan reported by HealthVerity, (2) met the Centers for Disease Control and Prevention criteria for moderately or severely immunocompromised (HIV/AIDS or primary immunodeficiency, hematologic malignancy in the prior year, solid organ or bone marrow transplant in the prior two years, or use of immunosuppressive therapy in the prior 210 days), and (3) previously received at least one dose of COVID-19 vaccine. We calculated the cumulative incidence of 2023–2024 COVID-19 vaccine receipt through March 31, 2024, stratified by state, age group, and specific immunocompromising condition.</div></div><div><h3>Results</h3><div>A total of 321,896 (median age 55 years; 57 % female) and 43,250 (median age 45 years; 64 % female) immunocompromised individuals met selection criteria in California and Louisiana, respectively. In both states, the most common immunocompromising category was the use of immunosuppressive therapy (78 % and 85 % of individuals in California and Louisiana, respectively). Only 21 % of individuals in California and 6 % of individuals in Louisiana received a 2023–2024 COVID-19 vaccine by March 31, 2024. Uptake was similar across immunocompromising conditions.</div></div><div><h3>Discussion</h3><div>During the 2023–2024 respiratory virus season, COVID-19 vaccine uptake among the immunocompromised in these 2 states was low, with fewer than 21 % receiving a 2023–2024 dose. Enhanced efforts to increase COVID-19 vaccine uptake in this vulnerable population are needed.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127120"},"PeriodicalIF":4.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-23DOI: 10.1016/j.vaccine.2025.127144
Yoshikazu Honda-Okubo , Isaac G. Sakala , Lei Li , Helle Bielefeldt-Ohmann , Yuri S. Lebedin , Nikolai Petrovsky
{"title":"Advax®-adjuvanted inactivated influenza vaccine provides accelerated protection of mice via early induction of an influenza-specific IgM response","authors":"Yoshikazu Honda-Okubo , Isaac G. Sakala , Lei Li , Helle Bielefeldt-Ohmann , Yuri S. Lebedin , Nikolai Petrovsky","doi":"10.1016/j.vaccine.2025.127144","DOIUrl":"10.1016/j.vaccine.2025.127144","url":null,"abstract":"<div><div>It would be advantageous if a strategy could be found to accelerate vaccine induction of anti-influenza adaptive immunity to more rapidly protect frontline workers and other vulnerable individuals during virus outbreaks. This study asked whether Advax® delta inulin adjuvant could accelerate the kinetics of protection afforded by a single dose of inactivated influenza vaccine (IIV) in two different strains of mice. A single dose of Advax®-adjuvanted IIV, but not IIV alone, gave complete protection if given 7 or 3 days before, and even when given at the same time as virus challenge (same day protection). Co-administration of both IIV and Advax® were critical to obtaining robust same day protection which was not seen with the individual vaccine components. Same day protection was lost in B-cell deficient μMT mice but was still evident in T cell-depleted mice, confirming its dependence on humoral but not T cell immunity. Day 6 post-challenge serum from protected mice demonstrated elevated influenza-binding IgM which had hemagglutination inhibition activity not seen in mice that received IIV alone. This confirmed that Advax® accelerated the kinetics of anti-influenza IgM production in response to IIV. Influenza protection could be transferred to naïve mice using day 6 sera or purified IgM from Advax®-adjuvanted IIV-immunised mice. Draining lymph nodes from protected mice showed increased CD138<sup>+</sup> B220<sup>+</sup> migratory and IgM<sup>+</sup> extrafollicular, antibody secreting cells. These results show Advax® adjuvant accelerates the kinetics of anti-influenza IgM production in response to IIV thereby enabling the vaccine to protect against an infection acquired at the same time as the immunisation. While further studies are required to confirm that this ability to accelerate humoral immune kinetics extends to other species, including non-human primates, the phenomenon of adjuvant-accelerated IIV protection offers promise as a strategy for development of faster-acting vaccines.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127144"},"PeriodicalIF":4.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143863772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-22DOI: 10.1016/j.vaccine.2025.127167
Pengju Xu , Jiangao Lu , Lijun Chen , Xiaopeng Chen , Zhipei Lu , Maochun Ye , Xuying Wang , Kang Ouyang , Yeshi Yin , Ying Chen , Zuzhang Wei , Weijian Huang , Yifeng Qin
{"title":"Development of a chicken egg yolk antibody (IgY) could effectively prevent and treat goose astrovirus infection","authors":"Pengju Xu , Jiangao Lu , Lijun Chen , Xiaopeng Chen , Zhipei Lu , Maochun Ye , Xuying Wang , Kang Ouyang , Yeshi Yin , Ying Chen , Zuzhang Wei , Weijian Huang , Yifeng Qin","doi":"10.1016/j.vaccine.2025.127167","DOIUrl":"10.1016/j.vaccine.2025.127167","url":null,"abstract":"<div><div>Goose astrovirus (GAstV) is a major threat to the goose industry, with no effective drugs or vaccines available. Developing safe and effective prevention and treatment strategies is essential to reduce its impact. In our study, we used the GAstV GDCS strain as the vaccine antigen and found that a 1 ‰ formaldehyde concentration effectively inactivated the virus after 24 h at 37 °C. The inactivated virus antigen was subsequently emulsified with white oil to formulate the GAstV inactivated vaccine. This vaccine was administered four times to 22-week-old laying hens, and IgY was subsequently purified from the egg yolk using the polyethylene glycol (PEG) precipitation method. After the fourth immunization, IgY concentration was 3.133 mg/mL. SDS-PAGE showed IgY has a 65 kDa heavy chain and a 25 kDa light chain. The IgY effectively neutralized GAstV in vitro with a titer of up to 2^9.67. Administering IgY to goslings effectively prevents and treats GAstV infection by reducing symptoms, mortality, tissue damage, and viral load. These findings offer significant tools for the clinical prevention and management of GAstV infection.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127167"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-22DOI: 10.1016/j.vaccine.2025.127156
Xiaojian Zhang , Hua Shi , Ted M. Ross
{"title":"Multivalent H3 COBRA-based influenza vaccine elicits enhanced immune response in a pre-immune elderly ferret model","authors":"Xiaojian Zhang , Hua Shi , Ted M. Ross","doi":"10.1016/j.vaccine.2025.127156","DOIUrl":"10.1016/j.vaccine.2025.127156","url":null,"abstract":"<div><div>Influenza viruses cause significant mortality in humans, especially among people 65 years and older. The outbreaks of A(H3N2) influenza viruses or viruses of vaccine-mismatched strains are usually associated with more severe diseases in elderly population. Vaccination is the practical countermeasure for controlling influenza virus infection in humans. However, the immune responses elicited by current influenza vaccines in elderly are not as robust as those responses elicited in younger adults. There is an urgent need for a universal influenza virus vaccine that can induce broadly protective immunity against viral infection in elderly individuals. Currently, influenza virus vaccines that target conserved epitopes on a variety of influenza virus antigens are under evaluation. However, almost all these vaccine candidates are evaluated in adult animal models. In this study, we evaluated Computationally Optimized Broadly Reactive Antigen (COBRA)-based influenza vaccines in elderly ferrets with pre-existing immunity to historical influenza viruses to assess the breadth of vaccine induced protective antibody responses. Vaccination of elderly ferrets with Infectimune® adjuvanted mixtures of COBRA hemagglutinin (HA) and neuraminidase (NA) recombinant protein vaccines elicited robust binding antibodies against all components in the vaccine. Vaccine formulations with multiple H3 COBRA HA components significantly enhanced hemagglutination-inhibition (HAI) activity against H3N2 viruses. In addition, elderly ferrets vaccinated with multivalent COBRA HA and NA vaccines were protected from infection with reduced nasal virus shedding. Overall, a multivalent COBRA HA and NA vaccine may be an effective vaccine strategy to reduce morbidity and mortality in the elderly.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127156"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-22DOI: 10.1016/j.vaccine.2025.127143
Md. Din Islam , M. Monirul Islam , Ayae Inoue , Sanjida Yesmin , Subbaian Brindha , Takahiro Yoshizue , Hiromichi Tsurui , Takeshi Kurosu , Yutaka Kuroda
{"title":"Neutralizing antibodies against the Japanese encephalitis virus are produced by a 12 kDa E. coli- expressed envelope protein domain III (EDIII) tagged with a solubility-controlling peptide","authors":"Md. Din Islam , M. Monirul Islam , Ayae Inoue , Sanjida Yesmin , Subbaian Brindha , Takahiro Yoshizue , Hiromichi Tsurui , Takeshi Kurosu , Yutaka Kuroda","doi":"10.1016/j.vaccine.2025.127143","DOIUrl":"10.1016/j.vaccine.2025.127143","url":null,"abstract":"<div><div><em>Escherichia coli</em> is a powerful and cost-effective platform for producing recombinant proteins. However, <em>E. coli</em>- produced proteins lack side-chain glycosylation and may be misfolded due to non-native disulfide bonds, often leading to poor immunogenicity. As a result, they are commonly perceived as unsuitable for use as antiviral vaccine antigens. This study addresses this challenge using the small 12 kDa envelope protein domain III of the Japanese encephalitis virus (JEV-EDIII) as a model. We demonstrate that the low immunogenicity of <em>E. coli</em>- produced proteins can be effectively overcome by employing a solubility-controlling peptide tag (SCP-tag) composed of five isoleucines (C5I). <em>E. coli</em>-produced JEV-EDIII oligomerized into 100 nm (<em>R</em>h) soluble oligomers upon attachment of the C5I-tag, whereas the untagged JEV-EDIII remained monomeric (<em>R</em>h ∼ 1.9 nm). The C5I-tag significantly enhanced anti-JEV EDIII IgG titers, as evidenced by ELISA, and increased the population of memory T cells in the spleen, as assessed by flow cytometry. Most notably, the C5I-tagged JEV-EDIII elicited neutralizing antibodies, confirmed by the FRNT<sub>50</sub> neutralization assay using live JEV. These findings suggest that oligomerization via SCP-tagging offers a promising, adjuvant-free approach for producing neutralizing antibodies with long-term T cell memory, paving the way for developing <em>E. coli</em>- produced, protein domain-based vaccines.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127143"},"PeriodicalIF":4.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinePub Date : 2025-04-21DOI: 10.1016/j.vaccine.2025.127157
Joel Finney , Masayuki Kuraoka , Shengli Song , Akiko Watanabe , Xiaoe Liang , Dongmei Liao , M. Anthony Moody , Emmanuel B. Walter , Stephen C. Harrison , Garnett Kelsoe
{"title":"Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases","authors":"Joel Finney , Masayuki Kuraoka , Shengli Song , Akiko Watanabe , Xiaoe Liang , Dongmei Liao , M. Anthony Moody , Emmanuel B. Walter , Stephen C. Harrison , Garnett Kelsoe","doi":"10.1016/j.vaccine.2025.127157","DOIUrl":"10.1016/j.vaccine.2025.127157","url":null,"abstract":"<div><div>The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface. The cell lines are barcoded with fluorescent proteins, enabling high-throughput, 16-plex analyses of antibody binding with commonly available flow cytometers. The cell lines were at least as efficient as a Luminex multiplex binding assay at identifying NA antibodies from a library of unselected clonal IgGs derived from human memory B cells. The cell lines were also useful for measuring the magnitude and breadth of the serum antibody response elicited by experimental infection of rhesus macaques with influenza virus. The membrane-anchored NAs are catalytically active and are compatible with established sialidase activity assays. NA-expressing K530 cell lines therefore represent a useful tool for studying NA immunity and evaluating influenza vaccine efficacy.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"56 ","pages":"Article 127157"},"PeriodicalIF":4.5,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}