An exploratory analysis of the response to ChAdOx1 nCoV-19 (AZD1222) vaccine in males and females.
An exploratory analysis of the response to ChAdOx1 nCoV-19 (AZD1222) vaccine in males and females.
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DOI：
10.1016/j.ebiom.2022.104128
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发表时间：
2022-07
期刊：
影响因子：
11.1
通讯作者：
Voysey, Merryn
中科院分区：
文献类型：
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作者：
Marchevsky, Natalie Gabrielle;Li, Grace;Aley, Parvinder;Clemens, Sue Ann Costa;Barrett, Jordan Richard;Belij-Rammerstorfer, Sandra;Bibi, Sagida;Clutterbuck, Elizabeth;Dold, Christina;Felle, Sally;Flaxman, Amy;Folegatti, Pedro;Jenkin, Daniel;Gilbert, Sarah;Kelly, Sarah;Lambe, Teresa;Plested, Emma;Ramasamy, Maheshi;Singh, Nisha;Smith, Holly;Taylor, Stephen;Weckx, Lily;Pollard, Andrew John;Voysey, Merryn
已知不同性别的疫苗反应原性和免疫原性存在差异。已证明，在接种几种不同疫苗后，雌性动物报告的反应原性更高，产生的体液和细胞免疫应答高于雄性动物。目前尚不清楚COVID-19疫苗的情况是否也是如此，因为按性别分列的COVID-19疫苗研究数据并未定期报告。因此，我们评估了性别对COVID-19疫苗ChAdOx 1 nCoV-19的反应原性、免疫原性和有效性的影响。在巴西和英国进行的ChAdOx 1 nCoV-19单盲随机对照试验中，对15169名志愿者进行了疫苗有效性评估，主要终点定义为核酸扩增试验（NAAT）阳性的症状性SARS-CoV-2感染。所有参与者都被电子随机分配接受两个标准剂量的疫苗或对照产品。拟合逻辑回归模型以探索年龄和性别对反应原性的影响，并拟合线性模型以对数转换免疫原性数据的值。反应原性数据来自788名试验参与者的自我报告日记。748名参与者提供了假病毒中和试验数据，1543名参与者提供了抗SARS-CoV-2加标IgG试验数据。7619名参与者接受ChAdOx 1 nCoV-19，7550名接受对照。两剂ChAdOx 1 nCoV-19后，受试者（4243名女性和3376名男性）的疫苗有效性在男性中为66.1%（95% CI 55.9-73.9%），在女性中为59.9%（95% CI 49.8-67.9%）;没有证据表明两种性别之间的有效性存在差异（疫苗与性别相互作用项P=0.3359）。观察到抗加标IgG存在较小的统计学显著性差异（校正GMR 1.14; 95% CI 1.04-1.26），雌性动物的滴度高于雄性动物，但其他免疫学终点无统计学显著性差异。虽然大多数个体在ChAdOx 1 nCoV-19首次给药后报告至少1次全身反应，但女性在首次给药后报告任何全身反应的可能性是男性的两倍（OR 1.95; 95% CI 1.37-2.77）。首次给药后，5%的雌性和1%的雄性报告了38 ℃或以上的发热。头痛和疲劳是两种性别中最常报告的反应。我们的研究结果表明，没有证据表明COVID-19疫苗ChAdOx 1 nCoV-19在男性和女性中的有效性存在差异。雌性动物中更高的反应原性与疫苗效力的任何差异无关。研究注册于ISRCTN 90906759（COV 002）和ISRCTN 89951424（COV 003），随访正在进行中。资金来自英国研究与创新，工程和物理科学研究理事会，国家卫生研究所，流行病防范创新联盟，国家卫生研究所牛津生物医学研究中心，中国医学科学院医学科学创新基金，泰晤士河谷和南米德兰兹NIHR临床研究网络，莱曼基金会，雷德德奥尔，布拉瓦和特勒斯基金会、巴西尼韦尔上级佩索阿尔协调会和阿斯利康。
There are known differences in vaccine reactogenicity and immunogenicity by sex. Females have been shown to report greater reactogenicity and generate higher humoral and cellular immune responses than males following vaccination with several different vaccines. Whether this is also the case for COVID-19 vaccines is currently unknown, as COVID-19 vaccine study data disaggregated by sex are not routinely reported. Therefore, we have assessed the influence of sex on reactogenicity, immunogenicity and efficacy of COVID-19 vaccine ChAdOx1 nCoV-19. Vaccine efficacy was assessed in 15169 volunteers enrolled into single-blind randomised controlled trials of ChAdOx1 nCoV-19 in Brazil and the UK, with the primary endpoint defined as nucleic acid amplification test (NAAT)-positive symptomatic SARS-CoV-2 infection. All participants were electronically randomised to receive two standard doses of vaccine or the control product. Logistic regression models were fitted to explore the effect of age and sex on reactogenicity, and linear models fitted to log-transformed values for immunogenicity data. Reactogenicity data were taken from self-reported diaries of 788 trial participants. Pseudovirus neutralisation assay data were available from 748 participants and anti-SARS-CoV-2 spike IgG assay data from 1543 participants. 7619 participants received ChAdOx1 nCoV-19 and 7550 received the control. Vaccine efficacy in participants after two doses of ChAdOx1 nCoV-19 (4243 females and 3376 males) was 66.1% (95% CI 55.9-73.9%) in males and 59.9% (95% CI 49.8-67.9%) in females; with no evidence of a difference in efficacy between the sexes (vaccine by sex interaction term P=0.3359). A small, statistically significant difference in anti-spike IgG was observed (adjusted GMR 1.14; 95% CI 1.04-1.26), with higher titres in females than males, but there were no statistically significant differences in other immunological endpoints. Whilst the majority of individuals reported at least one systemic reaction following a first dose of ChAdOx1 nCoV-19, females were twice as likely as males to report any systemic reaction after a first dose (OR 1.95; 95% CI 1.37-2.77). Measured fever of 38°C or above was reported in 5% of females and 1% of males following first doses. Headache and fatigue were the most commonly reported reactions in both sexes. Our results show that there is no evidence of difference in efficacy of the COVID-19 vaccine ChAdOx1 nCoV-19 in males and females. Greater reactogenicity in females was not associated with any difference in vaccine efficacy. Studies were registered with ISRCTN 90906759 (COV002) and ISRCTN 89951424 (COV003) and follow-up is ongoing. Funding was received from the UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil, and AstraZeneca.
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BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
影响因子：
7.8
作者：
Giefing-Kröll C;Berger P;Lepperdinger G;Grubeck-Loebenstein B
通讯作者：
Grubeck-Loebenstein B
DOI：
10.1056/nejmoa2105290
发表时间：
2021-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Falsey AR;Sobieszczyk ME;Hirsch I;Sproule S;Robb ML;Corey L;Neuzil KM;Hahn W;Hunt J;Mulligan MJ;McEvoy C;DeJesus E;Hassman M;Little SJ;Pahud BA;Durbin A;Pickrell P;Daar ES;Bush L;Solis J;Carr QO;Oyedele T;Buchbinder S;Cowden J;Vargas SL;Guerreros Benavides A;Call R;Keefer MC;Kirkpatrick BD;Pullman J;Tong T;Brewinski Isaacs M;Benkeser D;Janes HE;Nason MC;Green JA;Kelly EJ;Maaske J;Mueller N;Shoemaker K;Takas T;Marshall RP;Pangalos MN;Villafana T;Gonzalez-Lopez A;AstraZeneca AZD1222 Clinical Study Group
通讯作者：
AstraZeneca AZD1222 Clinical Study Group
影响因子：
5.2
作者：
Alguacil-Ramos, A. M.;Muelas-Tirado, J.;Lluch-Rodrigo, J. A.
通讯作者：
Lluch-Rodrigo, J. A.
DOI：
10.1128/cdli.7.1.111-113.2000
发表时间：
2000-01-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Atabani, S;Landucci, G;Forthal, DN
通讯作者：
Forthal, DN