Studies on the level of neutralizing antibodies produced by inactivated COVID-19 vaccines in the real world
Authors: Zhang Haiying , Jia Yuyuan , Ji Ying , Cong Xu , Liu Yan , Yang Ruifeng , Kong Xiangsha , Shi Yijun , Zhu Ling , Wang Zhenyu , Wang Wei , Fei Ran , Liu Feng , Lu Fengmin , Chen Hongsong , Rao Huiying 
Published: August 2021

Background

Although effective vaccines have been developed against COVID-19, the level of neutralizing antibodies (Nabs) induced after vaccination in the real world is still unknown. To evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China.

Methods and findings

Serum samples were collected from 1,335 people aged 18 and over who were vaccinated with COVID-19 inactivated vaccine in Peking University People’s Hospital from January 19 to June 23, 2021, for detection of COVID-19 antibodies. The WHO standard of SARS-CoV-2 NAbs was detected. The coefficients of variation between the detection results and the true values of the NAbs detected by the WHO standard were all lower than the WHO international standard 3% after the dilution of the original and the dilution of the theoretical concentrations of 500 IU/mL, 250 IU/mL, 125 IU/mL, 72.5 IU/mL, 36.25 IU/mL and 18.125 IU/mL. On day 11-70, the positive rate of NAbs against COVID-19 was 82% to 100%; From day 71 to 332, the positive rate of NAbs decreased to 27%. The level of NAbs was significantly higher at 3-8 Weeks than at 0-3 Weeks. There was a high linear correlation between NAbs and IgG antibodies in 1335 vaccinated patients. NAbs levels were decreased in 31 of 38 people (81.6%) at two time points after the second dose of vaccine. There was no significant difference in age between the group with increased and decreased neutralizing antibody levels (χ2 =-0.034, P>0.05). The positive rate of NAbs in the two-dose vaccine group (77.3%) was significantly higher than that in the one-dose group (18.1%), with statistical difference (χ2=312.590, P<0.001). A total of 206 people who were 11-70 days after receiving the second dose were tested and divided into three groups: 18-40 years old, 41-60 years old and >60 years old. The positive rates of NAbs in three groups (18-40 years old, 41-60 years old and >60 years old) were 95.14%, 78.43% and 81.8%, respectively. The positive rate of NAbs was significantly higher in 18-40 years old than in 41-60 years old (χ2=12.547, P <0.01). The titer of NAbs in 18-40 years old group was significantly higher than that in 41-60 years old group (t=-0.222, P <0.01). The positive rate of NAbs in male group (89.32%) was lower than in female (91.26%), but there was no significant difference (χ2=0.222, P >0.05).

Conclusions

The positive rate of NAbs was the highest from 10 to 70 days after the second dose of vaccine, and the positive rate gradually decreased as time went by. There was a high linear correlation between COVID-19 NAbs and IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age, but not by gender. The highest levels of NAbs were produced between shots 21 to 56 days apart, suggesting that 21 to 56 days between shots is suitable for vaccination.

Author summary

Why was this study done?

At present, the inactivated vaccines that have been approved to market in China have passed clinical trials to prove their effectiveness and safety. But the level of neutralizing antibodies induced by vaccination in the real world remains unclear.

Serological testing for neutralizing antibodies against COVID-19 is important for assessing vaccine and treatment responses and comparing multiple drug candidates. We assessed the levels of neutralizing antibodies produced in populations receiving inactivated vaccines and assessed the persistence of these vaccines in producing COVID-19 neutralizing antibodies in healthy adults.

What did the researchers do and find?

We collected serum samples from 1,335 people aged 18 and above who had received COVID-19 vaccine in Peking University People’s Hospital, and divided them into two groups according to one dose of inactivated vaccine and two doses of inactivated vaccine.

Our study found that the positive rate of NAbs was 66.2% in adults who received one or two doses of inactivated vaccine and 77.3% in adults who received two doses of inactivated vaccine in the real world.

From 11 to 70 days after the second dose of vaccine, the positive rate of neutralizing antibodies against COVID-19 was 82-100%; On days 71-332, the positive rate of neutralizing antibodies decreased to 27%.

The titer and the positive rate of NAbs in 18-40 years old group were significantly higher than that in 41-60 years old group.

What do these findings mean?

What is novel is we observed that in the real world, the positive rate of neutralization antibody was the highest at 10 to 70 days after the second vaccination, and with the extension of the vaccination time, the positive rate of antibody gradually decreased. Therefore, we recommend that the third dose of vaccine be administered at day 61 to day 70 for COVID-19 neutralizing antibodies levels.

We observed that there was a high linear correlation between COVID-19 neutralization antibodies and COVID-19 IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, COVID-19 IgM/IgG antibodies can be detected instead.

In our manuscript, we found that the titer and positive rate of neutralizing antibodies in 18-40 years old group were higher than those in 41-60 years old group. The level of neutralizing antibodies produced after vaccination was affected by age, but not by gender.

We also observed that the highest levels of NAbs were produced between shots 21 to 35 days apart, suggesting that 21 to 35 days between shots is suitable for vaccination.