key: cord-0880517-f30jldqd
authors: Yue, Lei; Xie, Tianhong; Yang, Ting; Zhou, Jian; Chen, Hongbo; Zhu, Hailian; Li, Hua; Xiang, Hong; Wang, Jie; Yang, Huijuan; Zhao, Hong; Wei, Xingchen; Zhang, Yuhao; Xie, Zhongping
title: A third booster dose may be necessary to mitigate neutralizing antibody fading after inoculation with two doses of an inactivated SARS‐CoV‐2 vaccine
date: 2021-09-22
journal: J Med Virol
DOI: 10.1002/jmv.27334
sha: ac277d061ddfaab16c408a0628bff038cc73d35a
doc_id: 880517
cord_uid: f30jldqd

Neutralizing antibodies in volunteers who received two doses of an inactivated SARS-CoV-2 vaccine deceased over several months. A three-dose procedure study suggested that the boost conferred by a third dose rescued the waning of neutralizing antibodies after the two doses of the inactivated vaccine. Importantly, a booster dose can also elicit a more robust neutralizing antibody response than the two-dose procedure. This article is protected by copyright. All rights reserved.

A third booster dose may be necessary to mitigate neutralizing antibody fading after inoculation with two doses of an inactivated SARS-CoV-2 vaccine Figure 1C ). For volunteers of both sexes, those who received vaccines according to different immunization procedures and different age groups, serum neutralizing antibody titers at 8 months after the second dose were significantly lower than those at 1 month after the second dose. Moreover, at the same time point after the second dose, no significant differences in titers were noted regardless of sex, vaccine immunization procedure, and age. These results indicated that the reduction in serum neutralizing antibody titers was not affected by sex, vaccine immunization procedure, or age ( Figures 1E, 1G, and 1I ).

Due to the need to further explore COVID-19 vaccines, 67 persons in the above cohort voluntarily received a third dose ( Figure 1B) . One month after the third dose, serum neutralizing antibody titers were tested, and the positive conversion rate of antibodies increased to 95.5% (the positive conversion rates of the 67 patients were 86.6% at 1 month after the second dose and 65.7% at 8 months after the second dose) ( Figure 1D ). To our surprise, for these volunteers, the titers were not only significantly higher than those at 8 months after the second dose but were also significantly higher than those at 1 month after the second dose ( Figure 1D ). The titers were also not affected by sex, vaccine immunization procedure, or age ( Figures 1F, 1H, and 1J) . These results demonstrate that the booster dose of the vaccine (the third dose) can reverse the decrease in neutralizing antibodies after the second dose. Moreover, in terms of neutralizing antibody levels, the effect of a three-dose immunization procedure was significantly better than that of the two-dose immunization procedure. Importantly, these findings were not affected by sex, vaccine immunization procedure, or age. It is good news for a special population who need the third enhancer dose. As if so, it is not necessary to set up different vaccination strategies under emergency use. Of course, these results should be confirmed by large-scale clinical studies.

In addition, although a recent study reported that immune memory was still active at six months after the second dose, 8 more research is needed to confirm this finding and fully elucidate the underlying immunological principles. First, to prove whether this phenomenon is specific to inactivated vaccines, related data on the immune persistence and effectiveness of mRNA vaccines, adenovirus vaccines, and subunit vaccines are needed. Second, some studies have reported the immune memory characteristics of convalescent patients 9 , some studies have compared the characteristics of antibody responses in asymptomatic and symptomatic infected people or convalescent patients, 10, 11 and some researchers have demonstrated that memory plasma cells in bone marrow may play a key role in immune persistence. 12 The characteristics of the immune system after vaccination are still unclear, and in-depth studies on antibody responses and cellular immunity after two-dose and three-dose vaccination strategies are needed. In addition, this study was based on data from volunteers. Compared with large-scale clinical studies,

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