Effect of Heterologous Vaccination Strategy on Humoral Response against COVID-19 with CoronaVac plus BNT162b2: A Prospective Cohort Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Vaccine Information
2.2.1. Inactivated SARS-CoV-2 Vaccine by Sinovac (CoronaVacTM)
2.2.2. BNT162b2 mRNA Vaccine by Pfizer & BioNTech (Comirnaty®)
2.2.3. Mixed Vaccine Administration
2.3. Immune Response Assessments
- -
- Cohort-I (CV/CV) included those who received only two doses of CoronaVac (n = 50);
- -
- Cohort-II (CV/CV/CV) included those who received three doses of CoronaVac (n = 17);
- -
- Cohort-III (CV/CV/BNT) included those who received two doses (prime) of CoronaVac followed by the third dose (booster) with BNT162b2 (n = 168).
2.4. Statistical Analyses
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Vaccine Cohorts | |||
---|---|---|---|
n (%) or Mean ± Standard Deviation (Min-Max) | |||
Characteristics | Cohort-I | Cohort-II | Cohort-III |
Sex | |||
Male | 24 (24.5) | 7 (7.1) | 67 (68.4) |
Female | 26 (19.0) | 10 (7.3) | 101 (73.7) |
Chronic disease present | |||
Yes | 11 (18.0) | 4 (6.6) | 46 (75.4) |
No | 38 (22.0) | 13 (7.5) | 122 (70.5) |
History of COVID-19 infection | |||
Never | 42 (22.0) | 12 (6.3) | 137 (71.7) |
Before the 1st dose | 6 (16.2) | 5 (13.5) | 26 (70.3) |
After the 2nd dose | 2 (28.6) | 0 (0) | 7 (71.4) |
Age | 35.66 ± 8.13 | 39.29 ± 8.18 | 40.67 ± 10.94 |
Interval between | 148.35 ± 15.32 | 142.85 ± 10.48 | |
2nd and 3rd doses (days) | (136–180) | (136–186) | |
Interval between | 39.52 ± 10.50 | 45.92 ± 12.47 | |
2nd dose and blood sampling (days) | (18–50) | (18–71) |
Anti-S-RBD IgG (AU/mL) | Antibody Proportions | Humoral Immune Response | ||||||
---|---|---|---|---|---|---|---|---|
Vaccine Cohorts | 1st Month | 3rd Month | 6th Month | p | 6th/1st a | 6th/3rd b | N/R (%) c | |
Cohort-I n = 42 | Mean | 44.38 | 23.47 | 11.14 | ||||
S.D. | 49.84 | 40.51 | 24.97 | <0.001 | 0.64 | 0.40 | 16.7/83.3 | |
Median | 27.57 | 7.53 | 2.66 | |||||
Range | 203.73 | 229.62 | 119.14 | |||||
Cohort-II n = 12 | Mean | 46.61 | 15.02 | 76.18 | ||||
S.D. | 55.53 | 15.65 | 53.28 | 0.003 | 3.53 | 5.13 | 0/100.0 | |
Median | 13.99 | 8.61 | 85.99 | |||||
Range | 158.16 | 55.46 | 139.06 | |||||
Cohort-III n = 137 | Mean | 42.34 | 17.59 | 136.82 | ||||
S.D. | 37.73 | 27.17 | 11.00 | <0.001 | 17.00 | 20.44 | 0/100.0 | |
Median | 29.63 | 9.21 | 139.20 | |||||
Range | 146.10 | 214.71 | 116.40 |
Total Anti-Spike/Anti-Nucleocapsid IgG | Antibody Proportions | Humoral Immune Response | ||||||
---|---|---|---|---|---|---|---|---|
Vaccine Cohort | 1st Month | 3rd Month | 6th Month | p | 6th/1st a | 6th/3rd b | N/R (%) c | |
Cohort-I n = 42 | Mean | 30.26 | 22.72 | 1.91 | ||||
S.D. | 38.68 | 45.32 | 3.77 | <0.001 | 0.30 | 0.09 | 71.4/28.6 | |
Median | 11.98 | 3.39 | 0.054 | |||||
Range | 143.02 | 251.08 | 15.80 | |||||
Cohort-II n = 12 | Mean | 12.81 | 9.92 | 22.01 | ||||
S.D. | 11.36 | 12.82 | 28.64 | 0.035 | 4.15 | 3.58 | 16.7/83.3 | |
Median | 10.60 | 2.85 | 9.42 | |||||
Range | 35.05 | 36.69 | 89.43 | |||||
Cohort-III n = 137 | Mean | 27.74 | 19.01 | 1.82 | ||||
S.D. | 44.08 | 49.10 | 5.64 | <0.001 | 0.10 | 0.13 | 75.2/24.8 | |
Median | 10.88 | 3.82 | 0.062 | |||||
Range | 367.68 | 407.32 | 40.72 |
Anti-S-RBD IgG Levels | Antibody Proportions | |||||||
---|---|---|---|---|---|---|---|---|
Vaccine Cohorts | COVID-19 History | 1st Month | 3rd Month | 6th Month | p | 6th/1st a | 6th/3rd b | |
Cohort-I | No (n = 42) | Mean | 44.38 | 23.47 | 11.14 | |||
S.D. | 49.84 | 40.51 | 24.97 | <0.001 | 0.47 e | 0.39 f | ||
Median | 27.57 | 7.53 | 2.66 | |||||
Range | 203.73 | 229.62 | 119.14 | |||||
Yes, before the 1st dose | Mean | 31.71 | 42.23 | 13 | ||||
(n = 6) | S.D. | 14.44 | 34.36 | 10.56 | 0.135 | 0.49 | 0.47 | |
90.0 ± 46 (30–150) c | Median | 33.15 | 26.45 | 8.51 | ||||
days before the 1st dose | Range | 30.51 | 85.11 | 28.17 | ||||
Yes, after the 2nd dose | Mean | 33.03 | 329.7 | 118.9 | ||||
(n = 2) d | S.D. | 24.52 | 116.81 | 23.75 | 0.135 | 4.6 | 0.37 | |
55.0 ± 21.21 (40–70) d | Median | 33.03 | 329.7 | 118.9 | ||||
days after the 2nd dose | Range | 34.68 | 165.2 | 33.6 | ||||
Cohort-II | No | Mean | 46.61 | 15.02 | 76.18 | |||
(n = 12) | S.D. | 55.53 | 15.65 | 53.28 | 0.003 | 4.02 g | 6.44 h | |
Median | 13.99 | 8.61 | 85.99 | |||||
Range | 158.16 | 55.46 | 139.06 | |||||
Yes, before the 1st dose | Mean | 42.03 | 28.95 | 49.83 | ||||
(n = 5) | S.D. | 44.03 | 32.22 | 44.84 | 0.779 | 2.07 | 1.51 | |
98.60 ± 54.17 (43–180) c | Median | 14.68 | 19.4 | 45.12 | ||||
days before the 1st dose | Range | 95.35 | 81.26 | 101.51 | ||||
Cohort-III | No | Mean | 42.34 | 17.59 | 136.82 | |||
(n = 137) | S.D. | 37.73 | 27.17 | 11 | <0.001 | 19.68 j | 23.19 k | |
Median | 29.63 | 9.21 | 139.2 | |||||
Range | 146.1 | 214.71 | 116.4 | |||||
Yes, before the vaccinations | Mean | 66.28 | 42.41 | 137.7 | ||||
(n = 26) | S.D. | 69.09 | 45.71 | 4.74 | <0.001 | 5.33 | 8.89 | |
130.2 ± 91.31 (30–330) c | Median | 38.48 | 22.02 | 137.75 | ||||
days before the 1st dose | Range | 280.32 | 175.18 | 18.3 | ||||
Yes, between the 2nd and 3rd dose | Mean | 39.91 | 188 | 134.22 | ||||
(n = 5) | S.D. | 16.4 | 153.94 | 19.28 | 0.247 | 4.02 | 2.94 | |
88.0 ± 51.67 (60–180) d | Median | 33.41 | 248 | 142.7 | ||||
days after the 2nd dose | Range | 38.95 | 319.73 | 45.7 |
Vaccine Cohorts | Age (Years) | Anti-S-RBD IgG Levels | Antibody Proportions | |||||
---|---|---|---|---|---|---|---|---|
1st Month | 3rd Month | 6th Month | p | 6th/1st a | 6th/3rd b | |||
Cohort-I | 20–29 (n = 12) | Mean | 42.91 | 16.11 | 4.82 | |||
S.D. | 42.30 | 22.92 | 6.59 | <0.001 | 0.31 | 0.34 | ||
Median | 35.61 | 8.08 | 2.15 | |||||
Range | 129.93 | 84.31 | 24.01 | |||||
30–39 (n = 17) | Mean | 67.04 | 39.44 | 22.10 | ||||
S.D. | 61.91 | 57.35 | 36.72 | <0.001 | 0.27 | 0.47 | ||
Median | 48.64 | 25.63 | 6.26 | |||||
Range | 202.24 | 229.62 | 119.14 | |||||
40–49 (n = 11) | Mean | 15.17 | 9.77 | 2.74 | ||||
S.D. | 11.96 | 11.37 | 2.47 | <0.001 | 1.04 | 0.35 | ||
Median | 9.97 | 4.67 | 1.91 | |||||
Range | 34.04 | 38.40 | 8.21 | |||||
50 and older (n = 2) | Mean | 21.36 | 7.21 | 2.19 | ||||
S.D. | 14.70 | 3.84 | 1.07 | 0.135 | 0.11 | 0.30 | ||
Median | 21.36 | 7.21 | 2.19 | |||||
Range | 20.80 | 5.44 | 1.52 | |||||
Cohort-II | 20–29 (n = 2) | Mean | 98.43 | 32.31 | 94.41 | |||
S.D. | 89.32 | 33.96 | 53.71 | 0.223 | 1.20 | 4.57 | ||
Median | 98.43 | 32.31 | 94.41 | |||||
Range | 126.33 | 48.04 | 75.97 | |||||
30–39 (n = 5) | Mean | 28.70 | 10.52 | 99.12 | ||||
S.D. | 42.42 | 8.422 | 52.96 | 0.018 | 7.02 | 10.65 | ||
Median | 12.89 | 9.99 | 105.30 | |||||
Range | 99.98 | 20.39 | 135.69 | |||||
40–49 (n = 2) | Mean | 102.25 | 20.42 | 94.14 | ||||
S.D. | 18.30 | 9.71 | 36.56 | 0.223 | 0.96 | 5.67 | ||
Median | 102.25 | 20.42 | 94.14 | |||||
Range | 25.89 | 13.74 | 51.71 | |||||
50 and older (n = 3) | Mean | 4.80 | 5.90 | 13.81 | ||||
S.D. | 1.46 | 1.09 | 9.43 | 0.264 | 2.94 | 2.59 | ||
Median | 4.62 | 5.86 | 10.56 | |||||
Range | 2.92 | 2.18 | 18.00 | |||||
Cohort-III | 20–29 (n = 26) | Mean | 49.34 | 22.95 | 138.94 | |||
S.D. | 40.50 | 29.62 | 4.81 | <0.001 | 6.19 | 15.47 | ||
Median | 34.14 | 10.39 | 139.60 | |||||
Range | 140.81 | 121.32 | 17.00 | |||||
30–39 (n = 30) | Mean | 44.10 | 14.74 | 137.29 | ||||
S.D. | 36.72 | 17.40 | 7.14 | <0.001 | 7.64 | 18.98 | ||
Median | 29.95 | 9.08 | 138.10 | |||||
Range | 130.97 | 85.35 | 34.90 | |||||
40–49 (n = 43) | Mean | 45.97 | 13.72 | 137.92 | ||||
S.D. | 40.64 | 16.13 | 7.09 | <0.001 | 8.92 | 23.34 | ||
Median | 25.56 | 9.07 | 139.90 | |||||
Range | 127.45 | 96.56 | 40.90 | |||||
50 and older (n = 38) | Mean | 32.05 | 20.56 | 133.76 | ||||
S.D. | 32.12 | 39.18 | 17.82 | <0.001 | 50.61 | 30.49 | ||
Median | 17.88 | 7.93 | 138.15 | |||||
Range | 143.20 | 214.71 | 109.80 |
Adverse Events | Vaccine Administered as the Third Dose [n(line %)] | |
---|---|---|
Inactivated Vaccine (n:17) | mRNA Vaccine (n:168) | |
Total | 3 (2.5) | 116 (97.5) |
Rash at the injection site | 0 (0.0) | 13 (100.0) |
Pain at the injection site | 1 (0.9) | 113 (99.1) |
Swelling at the injection site | 1 (5.0) | 19 (95.0) |
Itching at the injection site | - | 9 (100.0) |
Hypoesthesia at the injection site | - | 2 (100.0) |
Induration at the injection site | - | 15 (100.0) |
Numbness in the vaccinated arm | - | 18 (100.0) |
Weakness | 2 (3.5) | 55 (96.5) |
Fatigue | - | 48 (100.0) |
Fever | - | 19 (100.0) |
Shake | - | 8 (100.0) |
Chest pain | - | 5 (100.0) |
Diarrhoea | - | 2 (100.0) |
Nausea | - | 7 (100.0) |
Vomiting | - | 2 (100.0) |
Headache | 1 (3.4) | 28 (96.6) |
Dizziness | 1 (3.7) | 26 (96.3) |
Vertigo | - | 10 (100.0) |
Muscle pain | - | 30 (100.0) |
Back pain | - | 21 (100.0) |
Joint pain | - | 23 (100.0) |
Cough | - | 2 (100.0) |
Sore throat | - | 2 (100.0) |
Dyspnea | - | 3 (100.0) |
Papule | - | - |
Abdominal pain | - | 1 (100.0) |
Loss of appetite | - | 6 (100.0) |
Palpitation | - | 6 (100.0) |
Anosmia | - | 1 (100.0) |
Loss of taste | - | - |
Rash in the skin/mucosa | - | - |
Numbness in the tongue | - | - |
Syncope | - | - |
Increased blood pressure | - | 1 (100.0) |
Decreased blood pressure | - | - |
Allergic reaction/urticaria | - | - |
Anaphylaxis/anaphylactoid reaction | - | - |
Neurological complications | - | - |
Lymphadenopathy | - | 3 (100.0) |
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Demirhindi, H.; Mete, B.; Tanir, F.; Kara, E.; Kibar, F.; Cetiner, S.; Candevir, A.; Akti, S.E. Effect of Heterologous Vaccination Strategy on Humoral Response against COVID-19 with CoronaVac plus BNT162b2: A Prospective Cohort Study. Vaccines 2022, 10, 687. https://doi.org/10.3390/vaccines10050687
Demirhindi H, Mete B, Tanir F, Kara E, Kibar F, Cetiner S, Candevir A, Akti SE. Effect of Heterologous Vaccination Strategy on Humoral Response against COVID-19 with CoronaVac plus BNT162b2: A Prospective Cohort Study. Vaccines. 2022; 10(5):687. https://doi.org/10.3390/vaccines10050687
Chicago/Turabian StyleDemirhindi, Hakan, Burak Mete, Ferdi Tanir, Ertan Kara, Filiz Kibar, Salih Cetiner, Aslihan Candevir, and Sukriye Ece Akti. 2022. "Effect of Heterologous Vaccination Strategy on Humoral Response against COVID-19 with CoronaVac plus BNT162b2: A Prospective Cohort Study" Vaccines 10, no. 5: 687. https://doi.org/10.3390/vaccines10050687
APA StyleDemirhindi, H., Mete, B., Tanir, F., Kara, E., Kibar, F., Cetiner, S., Candevir, A., & Akti, S. E. (2022). Effect of Heterologous Vaccination Strategy on Humoral Response against COVID-19 with CoronaVac plus BNT162b2: A Prospective Cohort Study. Vaccines, 10(5), 687. https://doi.org/10.3390/vaccines10050687