Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons

Ibrahim, Karim Yaqub; Moreira, Raquel Megale; Santos, Carolina Ferreira dos; Strabelli, Tânia Mara Varejão; Belizário, Juliana de Cássia; Pinto, Maria Isabel de Moraes; Marinho, Ana Karolina Barreto Berselli; Pereira, Juliana Marquezi; Mello, Liliane Saraiva de; Ando, Mauricio Cesar; Silva, Vitor Gabriel Lopes da; Sato, Paula Keiko; Lima, Marcos Alves de; França, João Italo Dias; Loch, Ana Paula; Miyaji, Karina Takesaki; Infante, Vanessa; Precioso, Alexander Roberto; Sartori, Ana Marli Christovam

doi:10.1590/S1678-9946202466024

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ORIGINAL ARTICLE • Rev. Inst. Med. trop. S. Paulo 66 • 2024 • https://doi.org/10.1590/S1678-9946202466024 copy

Immunogenicity of COVID-19 adsorbed inactivated vaccine (CoronaVac) and additional doses of mRNA BNT162b2 vaccine in immunocompromised adults compared with immunocompetent persons

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3^rd and 4^th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3^rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

KEYWORDS
Vaccine immunogenicity; COVID-19 vaccines; Inactivated vaccine; BNT162 vaccine; Immunocompromised host

	Immunocompromised (IC) (n=241)		Immunocompetent (H) (n=100)		p-value¹
Age (years)
Median (Q₁-Q₃)	36.0	(26.0 – 50.0)	37.0	(31.0 – 44.0)
Gender, n (%)					0.405
Female	129	(53.5)	48	(48.0)
Male	112	(46.5)	52	(52.0)
Ethnicity, n (%)					0.633
White	135	(56.0)	59	(59.0)
Non-white	106	(44.0)	41	(41.0)
Years of study					<0.001
Median (Q₁-Q₃)	11	(9 - 12)	15	(11 - 16)

	Immunocompromised (IC)			Immunocompetent (H)			p-value

	n	value	95%CI	n	value	95%CI
SPR,%
Basal	241	33.2	(27.3 – 39.5)	100	22.0	(14.3 – 31.4)	0.051
post-V1	231	38.5	(32.2 – 45.1)	100	27.0	(18.6 – 36.8)	0.046
post-V2	231	51.9	(45.3 – 58.5)	100	91.0	(83.6 – 95.8)	<0.001
pre-V3	.	.	.	86	77.9	(67.7 – 86.1)	.
post-V3	202	58.4	(51.3 – 65.3)	98	78.6	(69.1 – 86.2)	<0.001¹
pre-V4	184	67.9	(60.7 – 74.6)	.	.	.	0.113²
post-V4	172	67.4	(59.9 – 74.4)	.	.	.	0.068³
End	166	75.3	(68.0 – 81.7)	97	86.6	(78.2 – 92.7)	0.039
SCR,%
post-V1	231	16.9	(12.3 – 22.3)	100	13.0	(7.1 – 21.2)	0.415
post-V2	231	33.3	(27.3 – 39.8)	100	79.0	(69.7 – 86.5)	<0.001
pre-V3	.	.	.	86	65.1	(54.1 – 75.1)	.
post-V3	202	41.6	(34.7 – 48.7)	98	65.3	(55.0 – 74.6)	<0.001¹
pre-V4	184	52.7	(45.2 – 60.1)	.	.	.	0.065²
post-V4	172	51.7	(44.0 – 59.4)	.	.	.	0.041³
End	166	62.0	(54.2 – 69.5)	97	73.2	(63.2 – 81.7)	0.079
GMT
Basal	241	0.5	(0.4 – 0.8)	100	0.3	(0.2 – 0.5)	<0.001
post-V1	231	1.0	(0.7 – 1.5)	100	0.7	(0.4 – 1.2)	0.820
post-V2	231	2.3	(1.5 – 3.4)	100	15.1	(10.3 – 22.3)	<0.001
pre-V3	.	.	.	86	7.2	(4.5 – 11.5)	.
post-V3	202	2.8	(1.9 – 4.2)	98	10.0	(6.3 – 16.0)	<0.001¹
pre-V4	184	6.5	(4.3 – 9.8)	.	.	.	0.740²
post-V4	172	7.0	(4.6 – 10.7)	.	.	.	0.265³
End	166	10.6	(7.0 – 15.9)	97	33.6	(21.5 – 52.5)	<0.001
GMTR
post-V1	231	1.8	(1.5 – 2.1)	100	2.2	(1.8 – 2.7)	<0.001
post-V2	231	4.2	(3.2 – 5.5)	100	49.4	(32.0 – 76.3)	<0.001
pre-V3	.	.	.	86	25.9	(15.4 – 43.5)	.
post-V3	202	5.7	(4.1 – 7.8)	98	34.4	(19.9 – 59.3)	<0.001¹
pre-V4	184	13.6	(9.0 – 20.6)	.	.	.	0.028²
post-V4	172	13.1	(8.4 – 20.5)	.	.	.	0.004³
End	166	22.6	(14.8 – 34.7)	97	113.3	(60.5 – 212.3)	<0.001

	Immunocompromised (IC)			Immunocompetent (H)			p-value

	n	value	95%CI	n	value	95%CI
SPR,%
Basal	241	31.5	(25.7 – 37.8)	100	18.0	(11.0 – 26.9)	0.011
post-V1	231	45.9	(39.3 – 52.5)	100	42.0	(32.2 – 52.3)	0.548
post-V2	231	59.3	(52.7 – 65.7)	100	96.0	(90.1 – 98.9)	<0.001
pre-V3	.	.	.	86	55.8	(44.7 – 66.5)	.
post-V3	202	81.7	(75.6 – 86.8)	98	100.0	(96.3 – 100.0)	<0.001¹
pre-V4	184	85.9	(80.0 – 90.6)	.	.	.	<0.001²
post-V4	172	89.0	(83.3 – 93.2)	.	.	.	<0.001³
End	166	88.0	(82.0 – 92.5)	97	100.0	(96.3 – 100.0)	<0.001
SCR,%
post-V1	231	19.0	(14.2 – 24.7)	100	32.0	(23.0 – 42.1)	0.015
post-V2	231	33.8	(27.7 – 40.3)	100	86.0	(77.6 – 92.1)	<0.001
pre-V3	.	.	.	86	43.0	(32.4 – 54.2)	.
post-V3	202	71.3	(64.5 – 77.4)	98	99.0	(94.4 – 100.0)	0.006¹
pre-V4	184	72.8	(65.8 – 79.1)	.	.	.	<0.001²
post-V4	172	79.1	(72.2 – 84.9)	.	.	.	<0.001³
End	166	81.3	(74.6 – 86.9)	97	92.8	(85.7 – 97.0)	0.011
GMT
Basal	241	14.5	(10.9 – 19.3)	100	6.0	(4.3 – 8.3)	<0.001
post-V1	231	28.8	(21.1 – 39.3)	100	39.8	(28.8 – 54.9)	0.081
post-V2	231	58.8	(43.6 – 79.3)	100	213.2	(173.4 – 262.2)	<0.001
pre-V3	.	.	.	86	76.0	(51.9 – 111.4)	.
post-V3	202	393.2	(282.1 – 548.0)	98	1500.7	(1376.3 – 1636.3)	<0.001¹
pre-V4	184	401.8	(290.7 – 555.4)	.	.	.	<0.001²
post-V4	172	731.8	(542.5 – 987.2)	.	.	.	0.386³
End	166	730.0	(538.3 – 990.0)	97	1405.2	(1241.9 – 1590.1)	0.419
GMTR
post-V1	231	2.0	(1.7 – 2.3)	100	6.7	(5.5 – 8.2)	<0.001
post-V2	231	4.1	(3.2 – 5.1)	100	35.8	(26.2 – 48.8)	<0.001
pre-V3	.	.	.	86	13.2	(8.5 – 20.4)	.
post-V3	202	30.9	(21.8 – 43.8)	98	255.8	(183.8 – 356.1)	0.695¹
pre-V4	184	30.9	(21.5 – 44.6)	.	.	.	0.007²
post-V4	172	54.5	(37.4 – 79.4)	.	.	.	<0.001³
End	166	62.6	(43.4 – 90.2)	97	237.4	(160.6 – 350.8)	<0.001

	Immunocompromised (IC)			Immunocompetent (H)			p-value

	n	value	95%CI	n	value	95%CI
SPR,%
Basal	241	45.2	(38.8 – 51.7)	100	22.0	(14.3 – 31.4)	<0.001
post-V1	231	60.6	(54.0 – 67.0)	100	90.0	(82.4 – 95.1)	<0.001
post-V2	231	78.4	(72.5 – 83.5)	100	100.0	(96.4 – 100.0)	<0.001
pre-V3	.	.	.	86	100.0	(95.8 – 100.0)	.
post-V3	202	92.1	(87.5 – 95.4)	98	100.0	(96.3 – 100.0)	0.002¹
pre-V4	184	94.0	(89.6 – 97.0)	.	.	.	0.019²
post-V4	172	96.5	(92.6 – 98.7)	.	.	.	0.090³
End	166	95.2	(90.7 – 97.9)	97	100.0	(96.3 – 100.0)	0.028
SCR,%
post-V1	231	25.5	(20.0 – 31.7)	100	75.0	(65.3 – 83.1)	<0.001
post-V2	231	48.5	(41.9 – 55.1)	100	85.0	(76.5 – 91.4)	<0.001
pre-V3	.	.	.	86	84.9	(75.5 – 91.7)	.
post-V3	202	68.3	(61.4 – 74.7)	98	85.7	(77.2 – 92.0)	0.002¹
pre-V4	184	70.7	(63.5 – 77.1)	.	.	.	0.015²
post-V4	172	72.7	(65.4 – 79.2)	.	.	.	0.015³
End	166	74.1	(66.7 – 80.6)	97	85.6	(77.0 – 91.9)	0.031
GMT
Basal	241	2.6	(1.8 – 3.8)	100	0.7	(0.5 – 1.2)	<0.001
post-V1	231	6.6	(4.4 – 9.8)	100	9.1	(6.0 – 14.0)	0.267
post-V2	231	22.4	(15.6 – 32.2)	100	168.0	(143.8 – 196.3)	<0.001
pre-V3	.	.	.	86	79.3	(61.4 – 102.6)	.
post-V3	202	97.4	(72.7 – 130.6)	98	250.0	(250.0 – 250.0)	0.008¹
pre-V4	184	116.7	(88.5 – 153.8)	.	.	.	<0.001²
post-V4	172	157.0	(125.3–196.7)	.	.	.	<0.001³
End	166	151.0	(117.3 – 194.3)	97	250.0	(250.0 – 250.0)	<0.001
GMTR
post-V1	231	2.5	(2.0 – 3.1)	100	12.2	(9.0 – 16.6)	<0.001
post-V2	231	8.6	(6.2 – 12.0)	100	224.1	(137.8 – 364.3)	<0.001
pre-V3	.	.	.	86	111.4	(67.7 – 183.4)	.
post-V3	202	41.7	(27.6 – 63.1)	98	340.8	(205.7 – 564.5)	0.001¹
pre-V4	184	50.5	(32.6 – 78.3)	.	.	.	0.263²
post-V4	172	60.4	(38.5 – 94.7)	.	.	.	<0.001³
End	166	66.1	(41.9 – 104.3)	97	338.8	(203.5 – 564.2)	<0.001

Variables	Immunocompromised (N=54)		Immunocompetent (N=42)

	N	%	n	%
Time of the COVID-19 episode*
<14 days after the 1^st vaccine dose	3	5.6	0	0.0
Post-V1	1	1.9	0	0.0
Post-V2	3	5.6	13	31.0
Post-V3	36	66.7	29	69.0
Post-V4	11	20.4	-	-
Symptomatic COVID-19	51	94.4	42	100.0
Healthcare use	38/51	70.4	40	95.2
Hospitalization	13/51	24.1	0	0.0
ICU	8/13	61.5	-	-
Intubation / mechanical ventilation	6/7	85.7	-	-
Non-invasive ventilation or high-flow catheter	6/7	85.7	-	-
Nasal catheter or mask	7/7	100.0	-	-
Oxygen	7/13	53.8	-	-
Vasoactive drugs	6/13	46.2	-	-
Dialysis	2/13	15.4	-	-
ECMO	1/13	7.7	-	-
COVID-19 outcome
Ongoing	1	1.9	0	0.0
Recovered	45	83.3	41	97.6
Recovered with sequelae	3	5.6	1	2.4
Not recovered	1	1.9	0	0.0
Death	4	7.4	0	0.0
Variant
P.1 SARS-COV-2	3	5.6	0	0.0
20J (GAMMA, V3) (P.1)	1	1.9	1	2.4
21J (DELTA) (AY.99.2)	0	0.0	2	4.8
21A (DELTA) (B.1.617.2)	1	1.9	3	7.1
21K (OMICRON)	2	3.7	1	2.4
21K (OMICRON) - (BA.1)	11	20.4	3	7.1
21K (OMICRON) - (BA.1.1)	3	5.6	4	9.5
21K (OMICRON) - (BA.1.1.1)	0	0.0	1	2.4
22A (OMICRON) - (BA.4)	2	3.7	5	11.9
22B (OMICRON) - (BA.5.2.1)	1	1.9	2	4.8
21L (OMICRON) - (BA.2)	4	7.4	2	4.8
21L (OMICRON) - (BA.2.47)	0	0.0	2	4.8
Other	3	5.6	9	21.4
Inconclusive	10	18.5	3	7.1
Not informed	13	24.1	4	9.5

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[1] Correspondence to: Karim Yaqub Ibrahim Universidade de São Paulo, Faculdade de Medicina, Hospital das Clinicas, Divisão de Moléstias Infecciosas e Parasitarias, R. Dr. Ovídio Pires de Campos, 225, Cerqueira César, CEP 05403-010, São Paulo, SP, Brazil Tel: +55 11 96327-9580 E-mail: karim.yaqub@hc.fm.usp.br