Immunological and pathological outcomes of SARS-CoV-2 challenge following formalin-inactivated vaccine in ferrets and rhesus macaques

被引：18

作者：

Bewley, Kevin R. ^{[1
]}

Gooch, Karen ^{[1
]}

Thomas, Kelly M. ^{[1
]}

Longet, Stephanie ^{[1
]}

Wiblin, Nathan ^{[1
]}

Hunter, Laura ^{[1
]}

Chan, Kin ^{[1
]}

Brown, Phillip ^{[1
]}

Russell, Rebecca A. ^{[2
]}

Ho, Catherine ^{[1
]}

Slack, Gillian ^{[1
]}

Humphries, Holly E. ^{[1
]}

Alden, Leonie ^{[1
]}

Allen, Lauren ^{[1
]}

Aram, Marilyn ^{[1
]}

Baker, Natalie ^{[1
]}

Brunt, Emily ^{[1
]}

Cobb, Rebecca ^{[1
]}

Fotheringham, Susan ^{[1
]}

Harris, Debbie ^{[1
]}

Kennard, Chelsea ^{[1
]}

Leung, Stephanie ^{[1
]}

Ryan, Kathryn ^{[1
]}

Tolley, Howard ^{[1
]}

Wand, Nadina ^{[1
]}

White, Andrew ^{[1
]}

Sibley, Laura ^{[1
]}

Sarfas, Charlotte ^{[1
]}

Pearson, Geoff ^{[1
]}

Rayner, Emma ^{[1
]}

Xue, Xiaochao ^{[2
]}

Lambe, Teresa ^{[3
]}

Charlton, Sue ^{[1
]}

Gilbert, Sarah ^{[3
]}

Sattentau, Quentin J. ^{[2
]}

Gleeson, Fergus ^{[4
]}

Hall, Yper ^{[1
]}

Funnell, Simon ^{[1
,5
]}

Sharpe, Sally ^{[1
]}

Salguero, Francisco J. ^{[1
]}

Gorringe, Andrew ^{[1
]}

Carroll, Miles ^{[1
,6
]}

机构：

[1] Publ Hlth England, Salisbury SP4 0JG, Wilts, England

[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[3] Univ Oxford, Jenner Inst, Nuffield Dept Med, Oxford OX3 7DQ, England

[4] Oxford Univ Hosp NHS Fdn Trust, Oxford Dept Radiol & Nucl Med, Oxford OX3 7LE, England

[5] Quadram Inst Biosci, Norwich Res Pk, Norwich, Norfolk, England

[6] Univ Oxford, Pandem Preparedness Ctr, Nuffield Dept Med, Oxford OX3 7LG, England

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 37期

关键词：

ACUTE RESPIRATORY SYNDROME; CORONAVIRUS VACCINE; VIRUS-INFECTION; BALB/C MICE; T-CELLS; DISEASE; GLYCOPROTEIN; IMMUNIZATION; ENHANCEMENT; ANTIBODIES;

D O I：

10.1126/sciadv.abg7996

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

There is an urgent requirement for safe and effective vaccines to prevent COVID-19. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferrets and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen 7 days after infection in ferrets. This increased lung pathology was observed at day 7 but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

引用

页数：17

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