Varun K. Phadke , Daniel J. Gromer , Paulina A. Rebolledo , Daniel S. Graciaa , Zanthia Wiley , Amy C. Sherman , Erin M. Scherer , Maranda Leary , Tigisty Girmay , Michele P. McCullough , Ji-Young Min , Stefania Capone , Andrea Sommella , Alessandra Vitelli , Jamie Retallick , Janine Seetahal , Mark Koller , Rachel Tsong , Hannah Neill-Gubitz , Mark J. Mulligan , Nadine G. Rouphael
{"title":"ChAd155 接种狂犬病疫苗与灭活的、纯化的鸡胚细胞狂犬病疫苗在健康成人中的安全性和免疫原性比较","authors":"Varun K. Phadke , Daniel J. Gromer , Paulina A. Rebolledo , Daniel S. Graciaa , Zanthia Wiley , Amy C. Sherman , Erin M. Scherer , Maranda Leary , Tigisty Girmay , Michele P. McCullough , Ji-Young Min , Stefania Capone , Andrea Sommella , Alessandra Vitelli , Jamie Retallick , Janine Seetahal , Mark Koller , Rachel Tsong , Hannah Neill-Gubitz , Mark J. Mulligan , Nadine G. Rouphael","doi":"10.1016/j.vaccine.2024.126441","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector.</div></div><div><h3>Methods</h3><div>We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies.</div></div><div><h3>Results</h3><div>Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers.</div></div><div><h3>Conclusions</h3><div>In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and immunogenicity of a ChAd155-vectored rabies vaccine compared with inactivated, purified chick embryo cell rabies vaccine in healthy adults\",\"authors\":\"Varun K. Phadke , Daniel J. Gromer , Paulina A. Rebolledo , Daniel S. Graciaa , Zanthia Wiley , Amy C. Sherman , Erin M. Scherer , Maranda Leary , Tigisty Girmay , Michele P. McCullough , Ji-Young Min , Stefania Capone , Andrea Sommella , Alessandra Vitelli , Jamie Retallick , Janine Seetahal , Mark Koller , Rachel Tsong , Hannah Neill-Gubitz , Mark J. Mulligan , Nadine G. Rouphael\",\"doi\":\"10.1016/j.vaccine.2024.126441\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector.</div></div><div><h3>Methods</h3><div>We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies.</div></div><div><h3>Results</h3><div>Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers.</div></div><div><h3>Conclusions</h3><div>In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity.</div></div>\",\"PeriodicalId\":23491,\"journal\":{\"name\":\"Vaccine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Vaccine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0264410X2401123X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0264410X2401123X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Safety and immunogenicity of a ChAd155-vectored rabies vaccine compared with inactivated, purified chick embryo cell rabies vaccine in healthy adults
Background
Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector.
Methods
We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies.
Results
Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers.
Conclusions
In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity.
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