Impact of vaccination on kinetics of neutralizing antibodies against SARS-CoV-2 by serum live neutralization test based on a prospective cohort

Figures & data

Figure 1. Study Enrolment and Outcomes (8 August 2021–24 October 2021).

Note: NAbs denotes neutralizing antibodies.

Table 1. Demographic characteristics and Vaccination history of the participants.

	Total participants (N = 576)	Breakthrough cases (n = 245)	Unvaccinated-infected cases (n = 331)	P
Age (Mean±SD)	50.7±18.4	46.7±11.7	53.7±16.0	<0.0001
Gender (n[%of total])				<0.0001
Female	391(67.9%)	187(76.3%)	204(61.6%)
Male	185(32.1%)	58(23.6%)	127(38.3%)
Vaccines (n[%of total])				---
BBIBP	43(7.5%)	43(17.6%)	---
CoronaVac	156(27.1%)	156(63.7%)	---
ZF2001	16(2.8%)	16(6.5%)	---
BBIBP&CoronaVac	30(5.2%)	30(12.2%)	---
Clinical classification (n[%of total])				<0.0001
Mild	112(19.4%)	42(17.1%)	70(21.1%)
Moderate	419(72.7%)	203(82.9%)	216(65.3%)
Severe/Critical	43(7.5%)	0(0%)	43(13.0%)
Untyped	2(0.3%)	0(0%)	2(0.6%)

Figure 2. Trends in NAb levels over time from 1 to 7 weeks of the onset/infection. (A) NAbs of the ancestral and Delta strains in breakthrough cases. (B) Neutralizing curves of the ancestral and Delta strains in breakthrough cases from 1 to 7 weeks of the onset/infection by live virus microneutralization assay. (C) NAbs of the ancestral and Delta strains in unvaccinated-infected cases. (D) Neutralizing curves of the ancestral and Delta strains in unvaccinated-infected cases from 1 to 7 weeks of the onset/infection by live virus microneutralization assay. ****P < 0.0001. (E) Trends of Ct value among different NAbs value over days after symptom onset/infection. Case1-3: breakthrough cases with high-medium-low NAb level, case4-6: unvaccinated-infected cases with high-medium-low NAb level.

Table 2. The geometric mean concentrations (U/mL) of the NAb against ancestral and Delta strains in breakthrough cases and unvaccinated-infected cases from 1–7 weeks after the onset/infection.

		Overall	1W	2W	3W	4W	5W	6W	7W
Breakthrough cases	N	660	21	108	193	177	116	37	8
	Ancestral	6793.8	964.2	7478.1	6843.6	5495.6	7489.4	6317.4	8304.5
	Delta	15268.2	1546.4	16511.1	16095.3	11620.5	17423.2	14612.5	19598.4
Unvaccinated-infected cases	N	772	12	227	87	136	156	114	40
	Ancestral	960.1	93.1	393.3	1335.1	1571.9	1557.9	1338.9	1636.1
	Delta	4108.1	179.9	1422.5	6476.5	6388.1	7294.9	6923.2	8594.2
P value of breakthrough cases VS. Unvaccinated-infected cases	Ancestral	<0.0001	0.053	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001
	Delta	<0.0001	0.142	<0.0001	<0.0001	<0.0001	<0.0001	<0.0001	0.001
GMC ratio of breakthrough/unvaccinated-infected	Ancestral	7.1	10.4	17.3	5.1	3.5	4.8	4.7	5.1
	Delta	3.7	8.6	10.7	2.5	1.8	2.4	2.1	2.3

Note: NAb denotes neutralizing antibody, GMC denotes geometric mean concentration, and W denotes week. Kruskal Wallis Test was used for the comparison of NAbs in the two groups.

Table 3. Viral clearance time and Ct value differences in different neutralizing antibody levels.

	Groups accortding to NAb titre (Median [IQR])
	High	Medium	Low	p value
Breakthrough cases
Viral clearance time (days)	19[16-23.25]	17.5[14-20.25]	17.5[11.5-19.75]	0.454
Ct value Max-Min	13[9.5-18]	19.5[14.5-21.5]	22[18.5-24.75]	0.047
Ct value Max-Min/Viral clearance time	0.69[0.45-1.07]	1.11[0.74-1.55]	1.38[1.01-1.89]	0.033
Unvaccinated-infected cases
Viral clearance time (days)	18[12-24.25]	11.5[9.5-15]	13[10.75-18.25]	0.267
Ct value Max-Min	19.5[14.75-26.25]	21.5[15.25-24]	20.5[19-23.75]	0.929
Ct value Max-Min/Viral clearance time	1.26[0.61-3.02]	1.64[1.21-2.50]	1.73[1.08-2]	0.605

Note: Ct denotes cycle threshold.

Figure 3. Kinetics of NAb according to clinical status. In breakthrough cases (A-C): (A) NAbs of the ancestral strain from 1-7 weeks of the onset/infection by live virus microneutralization assay. (B) NAbs of the Delta strain from 1-7 weeks of the onset/infection by live virus microneutralization assay. (C) NAbs of the ancestral and Delta strain. In un-vaccinated-infected cases (D-E): (D) NAbs of the ancestral strain from 1-7 weeks of the onset/infection by live virus microneutralization assay. (E) NAbs of the Delta strain from 1-7 weeks of the onset/infection by live virus microneutralization assay. (F) NAbs of the ancestral and Delta strain. Each circle represents the titer for a serum sample. ****P < 0.0001.

Figure 4. Impact of duration after SARS-CoV-2 vaccination on NAbs against ancestral and Delta variants in breakthrough cases. (A) Effect of SARS-CoV-2 vaccination duration on NAbs against the ancestral strain over weeks after onset/infection. (B) Effect of SARS-CoV-2 vaccination duration on NAbs against the Delta strain over weeks after onset/infection.

Figure 5. Neutralizing responses of three strains over time. (A) NAbs of the ancestral, Delta, and Omicron BA.5 in breakthrough cases. (B) Neutralizing curves of the ancestral, Delta, and Omicron BA.5 in breakthrough cases from 1 to 7 weeks of the onset/infection by live virus microneutralization assay. (C) NAbs of the ancestral, Delta, and Omicron BA.5 in unvaccinated-infected cases. Each circle represents the titre for a serum sample. (D) Neutralizing curves of the ancestral, Delta, and Omicron BA.5 in unvaccinated-infected cases from 1–7 weeks of the onset/infection by live virus microneutralization assay. ****P < 0.0001, ***P < 0.001, *P < 0.05, ns denotes no statistical differences.