Background 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. Methods 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. Findings 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. Conclusions 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. Funding 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. Graphical abstract Context and significance Many people around the world have received different types of COVID-19 vaccines in their two-dose vaccination schedules for various reasons. However, it is not clear whether the inoculation order of such heterologous vaccines was associated with subsequent immune responses. Here, an international team of physicians and scientists from China and the United States studied a cohort of healthcare workers who were among the earliest recipients of heterologous COVID-19 vaccination. The authors found that the inoculation order of heterologous vaccines was associated with the capability of neutralizing SARS-CoV-2 variants but not the original strain that the vaccines were based on. The results suggested that using heterologous booster vaccines with high potency could be a cost-efficient way to elicit protective immunity against future variants. Zhu et al. studied healthcare workers who had received homologous or heterologous prime-boost COVID-19 vaccination to find that the inoculation order of heterologous vaccines was associated with serum neutralization breadth against SARS-CoV-2 variants. The findings suggested using heterologous booster vaccines with high potency as a cost-efficient strategy against future variants.
【저자키워드】 COVID-19 vaccine, heterologous vaccination, SARS-CoV-2 variants, Neutralization antibody, antibody cross-reactivity, 【초록키워드】 SARS-CoV-2, vaccination, Vaccines, antibody, Influenza, technology, variant, SARS-CoV-2 variant, B.1.617.2, variants, healthcare worker, China, Neutralizing activity, Cohort, COVID-19 vaccination, protective immunity, immune responses, International, Program, Virus neutralization, Health care worker, Neutralizing, development, homologous, funding, mechanism, Heterologous, Pseudovirus neutralization assay, inactivated, Serum Neutralization, breadth, Booster vaccine, association, Evidence, Innovation, heterologous vaccine, PNA, heterologous prime-boost, Laboratory test, Science, natural, Abstract, Shenzhen, Multivariable regression, foundation, confounders, circulating, clinical evidence, finding, Department, physician, neutralization titer, recipient, significantly lower, Wuhan-Hu-1, vaccination schedule, veteran, Affect, Context, shown, the United State, subsequent, conducted, suggested, analysis, elicit, homologous or heterologous, the vaccine, Animal experiment, antibody response against, clinical observation, Commission, cost-efficient strategy, immunological analysis, 【제목키워드】 SARS-CoV-2, Vaccine, Neutralizing, breadth, heterologous prime-boost,