Laboratory of Clinical Immunology, Division of Laboratory Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
Center for Kidney Diseases, Department of Nephrology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China; Department of Biomedical Science, Shenzhen Research Institute, City University of Hong Kong, Kowloon Tong, Hong Kong, China.
Med. 2022 Aug 12;3(8):568-578.e3. doi: 10.1016/j.medj.2022.05.003. Epub 2022 Jun 9.
Emerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear.
We conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA.
We observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders.
Our data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism.
National Key R&D Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.
新出现的证据表明，异源加强 COVID-19 疫苗接种是一种优于同源方案的策略。动物实验和临床观察表明，异源接种后对流感变异体的抗体反应增强；然而，COVID-19 疫苗在加强方案中的接种顺序是否会影响对 SARS-CoV-2 变异体的抗体反应尚不清楚。
我们对最近通过同源或异源加强方案接种三种类型的灭活 COVID-19 疫苗的一组医护人员（n=486）进行了免疫分析。通过总抗体测量、替代病毒中和试验和假病毒中和试验（PNA）评估对原始 SARS-CoV-2（武汉-Hu-1）的抗体反应。此外，还通过 PNA 测量对 SARS-CoV-2 关注的变异体的血清中和活性。
我们观察到在接受异源 BBIBP-CorV/CoronaVac 和 WIBP-CorV/CoronaVac 的受种者中，对广泛传播的 SARS-CoV-2 变异体 B.1.617.2 表现出最强的血清中和活性。相比之下，接受 CoronaVac/BBIBP-CorV 和 CoronaVac/WIBP-CorV 的受种者对 B.1.617.2 的中和滴度明显低于接受反转方案的受种者。实验室检测表明，针对常见变异体的中和活性而不是针对原始 SARS-CoV-2 的中和活性与异源加强疫苗接种的接种顺序有关。在调整已知混杂因素后，多变量回归分析证实了这种关联。
我们的数据为异源加强疫苗接种受种者中针对 SARS-CoV-2 的中和广度依赖于接种顺序的扩展提供了临床证据，并呼吁进一步研究其潜在机制。
国家重点研发计划、国家发展和改革委员会、国家自然科学基金委员会、深圳市科技创新委员会和美国退伍军人事务部。
