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. 2022 May 3;28(8):662–680. doi: 10.1016/j.molmed.2022.04.012

Table 1.

Immunogenicity measures in maternal blood or cord blood samples after COVID-19 vaccination during pregnancya

Location and study dates Vaccines during pregnancy Number of pregnant women vaccinated Timing of vaccination during pregnancy Comparator groups Immune response measures Responses in womenb Responses in cord blood Placental antibody transfer Other results Assays used for antibody quantification Refs
Israel
January–March 2021
At least one dose
BNT162b2
86 First dose: 34.5 (±7.5) weeks GA 65 Women who had COVID-19 during pregnancy at 28.1 (±8.3) weeks GA
62 Unvaccinated uninfected pregnant women
Anti-RBD IgG and IgM; anti-S IgG and IgM
Reported as net fluorescence intensity
Robust IgG response by day 15 after the first dose, further increase in IgG responses after the second dose
At delivery, higher anti-S and anti-RBD IgG in vaccinated women than in infected women
IgG responses by day 15 after the first dose, further increase in IgG responses after second dose
Anti-S and anti-RBD IgG no different between the vaccinated and infected groups
IgM response in five samples from the infected group
Similar transfer profiles in the vaccinated and infected groups Association between maternal and cord blood IgG responses Milliplex MAP SARS-CoV-2 Antigen Panel, MerckMillipore [30]
Israel
January–February 2021
Two doses
BNT162b2
96
Tested 2 months following the second dose
2–40 weeks GA 96 Non-pregnant vaccinated women Anti-RBD IgG
Reported as signal to cutoff ratios
At 2 weeks to 2 months following the second dose
Overall: 100% positive
Pregnant: 27.03 (±10.72)
Non-pregnant: 34.35 (±10.25)
Not shown Not shown Anti-RBD IgG responses did not differ according to trimester of vaccination Access SARS-CoV-2 IgG assay, Beckman Coulter [31]
USA
December 2020–March 2021
Two doses
BNT162b2: 37%
mRNA-1273: 63%
30 Vaccinated: 16 lactating women; 57 non-pregnant nonlactating women
Previously infected: 6 non-pregnant women and 22 pregnant women
Anti-RBD IgG
Neutralization responses
Functional antibody responses
T cell responses
Binding, neutralizing, and functional non-neutralizing antibody responses, and CD4 and CD8 T cell responses were present in pregnant, lactating, and non-pregnant women following vaccination Binding and neutralizing antibodies were detected in cord blood Vaccinated group: anti-RBD IgG cord blood 19 873 vs. mother 14 953
Neutralizing antibody in cord blood 324 vs. mother 1016
Infected group: anti-RBD IgG cord blood 635 vs. mother 1342
Neutralizing antibody in cord blood 164 vs. mother 151
Descriptive statistics only In-house enzyme-linked immunosorbent assay [32]
USA
December 2020–March 2021
At least one dose
BNT162b2: 49%
mRNA-1273: 51%
84
Tested at baseline (v0), at the second dose (v1), at 2–6 weeks after the second dose (v2), and at delivery (v3)
First dose: 23.2 (16.3–32.1) weeks GA; 13% during the first trimester, 46% during the second trimester, 40% during the third trimester
From second dose to delivery 14 (IQR: 11–16) days
Vaccinated: 31 lactating women
16 non-pregnant women
37 Women who had COVID-19 during pregnancy at 4–12 weeks before delivery
Anti-S IgM, IgG, and IgA
Anti-RBD IgM, IgG, and IgA
Neutralization responses at v3
Reported as mean fluorescence intensity
Antibody responses were similar in pregnant/lactating women and nonpregnant women
Increase for all isotypes across all antigens from v0 to v1, further increase in IgG responses from v1 to v2
Spike responses increased quicker than RBD at v1 and v2
IgM and IgA responses were induced after first dose but not after second dose
Neutralizing antibody: 104.7 (IQR: 61.2–188.2)
100% positive anti-S and anti-RBD IgG
Neutralizing antibody: 52.3 (IQR: 11.7–69.6)
Not shown Placental transfer ratio of anti-S IgG (but not anti-RBD) positively correlated with time from second dose to delivery
No association between maternal responses and time of vaccination during pregnancy
Higher responses is vaccinated women compared to pregnant women with natural infection
Multiplexed Luminex assay, ThermoFisher [36]
Israel
February–March 2021
Two doses
BNT162b2
29 Third trimester 29 Women who had COVID-19 during pregnancy
21 Pregnant women not infected, not vaccinated
Anti-RBD IgG
Reported as U/ml
Not shown Vaccinated group: 100% positive; 224.7 U/ml (±64.3)
Infected group: 100% positive; 83.7 U/ml (±91.6)
Not shown Association between maternal and cord blood responses Elecsys Anti-SARS-CoV-2 S immunoassay, Roche Diagnostics [38]
Israel
May–July 2021
Two doses, ≥7 days before delivery
BNT162b2
129 Second trimester
First dose: 21.9 (±3.3) weeks GA; second dose: 24.9 (±3.3) weeks GA
From second dose to delivery 14.4 (±3.0) weeks
None Anti-RBD IgG
Reported as AU/ml
Overall: 100% positive
1185.2 AU/ml (range: 146.6–32415.1)
Overall: 100% positive; 3315.7 AU/ml (range: 350.1–17 643.5) Approximately 2.6 Association between maternal and cord blood responses
Maternal and cord blood responses correlated positively with GA at second dose
Maternal and cord blood responses correlated inversely with the time from second dose to delivery and with maternal age
SARS-CoV-2 IgG II Quant, Abbott [40]
USA
January–March 2021
At least one dose
BNT162b2: 64%
mRNA-1273: 18%
Unknown vaccine: 14%
Two doses: 74%
27 Third trimester
First dose: 33 (±2) weeks GA
None Anti-RBD IgG and IgM
Reported as AU/ml
96% positive anti-RBD IgG
56% positive anti-RBD IgM
89% positive anti-RBD IgG (negative cord bloods from two women who received their first dose <3 weeks before delivery); 0 positive anti-RBD IgM. 1.0 ± 0.6 Cord blood and placental transfer ratio of IgG associated positively with time from vaccination
Cord blood IgG response associated positively with having received second dose.
DXI Platform, Beckman Coulter [42]
Israel
February–March 2021
Two doses, ≥14 days before delivery
BNT162b2
64 Third trimesterS
econd dose 33.5 (±3.2) weeks GA
From second dose to delivery 21.7 (±11.0) days
11 Women who had COVID-19 during pregnancy at 92.5 (±75.8) days before delivery Anti-RBD IgG
Reported as signal to cutoff ratio
Vaccinated group: 100% positive; 26.1 (IQR: 22.0–39.7)
Infected group: 2.6 (IQR: 0.9–3.5).
Vaccinated group: 98.3% positive; 20.2 (IQR: 12.7–29.0)
Infected group cord blood: 3.3 (IQR: 0.5–4.6)
0.77 Association between maternal and cord blood responses
Maternal responses associated negatively with time from second dose to delivery (but no correlation with cord blood IgG levels)
Access SARS-CoV-2 IgG assay, Beckman Coulter [43]
USA
January–March 2021
At least one dose
BNT162b2: 70%
mRNA-1273: 30%
Two doses: 55%
122 Not shown None Anti-RBD IgG and IgM Overall: 71% IgG-positive, 16% IgG- plus IgM-positive, 13% no detectable response (all women delivered within 4 weeks of first dose)
By 4 weeks after first dose: 100% IgG-positive
Women who received 1 dose: 44% IgG-positive
Women who received 2 doses: 99% IgG-positive
Not shown Association between maternal and cord blood IgG responses
Placental transfer ratio correlated positively with the number of weeks from second dose to delivery
Maternal IgG responses increased week on week, from 2 weeks after first dose
Pylon 3D platform, ET HealthCare [44]
Israel
February 2021
Two doses
BNT162b2
20 Third trimester
From first dose to delivery 33 (IQR: 30–37) days
From second dose to delivery 11 (IQR: 9–15) days
None Anti-RBD IgG and IgM, and anti-S IgG
Reported as AU/ml
100% positive anti-S and anti-RBD IgG; 30% positive anti-RBD IgM
Anti-S IgG: 319 AU/ml (IQR: 211–1033)
Anti-RBD IgG 11 150 (IQR: 6154–17 575)
100% positive anti-S and anti-RBD IgG
0% positive anti-RBD IgM
Anti-S IgG: 193 AU/ml (IQR: 111–260)
Anti-RBD IgG 3494 (IQR: 1817–6163)
Anti-S IgG: 0.44 (IQR: 0.25–0.61)
Anti-RBD IgG: 0.34 (IQR: 0.27–0.56)
Association between maternal and cord blood anti-S and anti-RBD IgG responses
Cord blood anti-S and anti-RBD IgG were associated positively with time from first dose to delivery
Anti-spike IgG and anti-RBD IgM: Liaison, DiaSorin, Saluggia, Italy
Anti-RBD IgG: SARSCoV-2 IgG II Quant, Abbott
[46]
Israel
February–April 2021
Two doses
BNT162b2
171 Third trimester
Early third trimester (27–31 weeks GA): 49%
From first dose to delivery 71 (IQR: 63–79) days
Late third trimester (32–36 weeks GA)
From first dose to delivery 41 (IQR 34–50) days
None Anti-RBD IgG and IgM
Anti-S IgG
Neutralization responses reported as AU/ml
Overall: 100% positive anti-S and anti-RBD IgG
Early third trimester – anti-S IgG: 200 AU/ml (IQR: 143–296), anti-RBD IgG: 3980 AU/ml (IQR: 2414–7022), anti-RBD IgM: 0%
Late third trimester – anti-S IgG: 292 AU/ml (IQR: 209–963), anti-RBD IgG: 8506 AU/ml (IQR: 4601–15 094), anti-RBD IgM: 18%
Overall: 100% positive anti-S and anti-RBD IgG
0% positive anti-RBD IgM
Early third trimester: anti-RBD IgG: 9620 AU/ml (IQR: 5131–15 332)
Late third trimester: anti-RBD IgG: 6697 AU/ml (IQR: 3157–14 731)
Early third trimester – anti-S IgG: 1.3 (IQR: 1.1–1.6), anti-RBD IgG: 2.3 (IQR: 1.7–3.0), neutralization: 1.9 (IQR: 1.7–2.5)
Late third trimester – anti-S IgG: 0.9 (IQR: 0.6–1.1), anti-RBD IgG: 0.7 (IQR: 0.5–1.2), neutralization: 0.8 (IQR: 0.5–1.1)
Association between maternal and cord blood anti-S, anti-RBD IgG responses and neutralizing activity
Maternal anti-S and anti-RBD IgG responses associated negatively with time from first dose to delivery
Cord blood anti-RBD IgG and placental transfer ratio of anti-S, anti-RBD IgG and neutralizing activity higher after early vs. late third trimester vaccination, and were associated positively with time from first dose to delivery
Anti-spike IgG and anti-RBD IgM: Liaison, DiaSorin, Saluggia, Italy
Anti-RBD IgG: SARSCoV-2 IgG II Quant, Abbott
[45]
USA
July–October 2021
BNT162b2: 68%
mRNA-1273: 32%
77 First dose: 20–32 weeks GA
From first dose to delivery 85 (±46) days
12 Women who had COVID-19 during pregnancy at 20–32 weeks GA Anti-S IgG
Reported as optical density
Vaccinated group: 2.03 (±0.47)
Infected group: 0.65 (±0.76)
Vaccinated group: cord blood 2.17 (±0.50); at 2 months of age 1.29 (±0.53), 98% positive; at 6 months of age 0.33 (±0.46), 57% positive
Infected group: cord blood 1.00 (±0.83); at 6 months of age 0 (±0.01), 8% positive
Not shown Responses at 2 months of age correlated positively with maternal and cord blood responses In-house enzyme-linked immunosorbent assay [49]
Israel
May–July 2021
Two doses, ≥1 week before delivery
BNT162b2
28 Second trimester
Second dose: 26 (IQR: 14–34) weeks GA
From second dose to delivery 11.1 (IQR: 9.3–15) weeks
12 Women who had COVID-19 during pregnancy at 20.6 (IQR: 17.6–36.9) weeks before delivery Anti-S IgG
Reported as AU/ml
Vaccinated group: 145 AU/ml (IQR: 113–202)
Infected group: 41 AU/ml (IQR: 19–95)
Vaccinated group: 216 AU/ml (IQR: 155–316)
Infected group: 64 AU/ml (IQR: 23–219)
Vaccinated group: 1.48 (IQR: 1.18–1.82)
Infected group: 1.35 (IQR: 1.19–1.84)
Association between maternal and cord blood responses
No association between maternal responses and placental transfer ratio
No association between maternal responses and interval from vaccination to delivery
Placental transfer ratio correlated positively with birthweight
Anti-spike IgG, Liaison, DiaSorin, Saluggia, Italy [51]
Germany
Start date not reported–June 2021
At least 1 dose
BNT162b2: 72%
mRNA-1273: 28%
Two doses: 97%
36 First dose 6% during the first trimester, 83% during the second trimester, 11% during the third trimester
From second dose to delivery 13 (range: 5.9–24.9) weeks
None Anti-S IgG
Reported as U/ml
100% positive 100% positive Not shown Elecsys anti-SARS-CoV-2 assay, Roche Diagnostics [52]
USA
March–October 2021
At least one dose
BNT162b2: 75%
mRNA-1273: 22%
Ad26.COV2.S: 2%
Two doses: 89%
Booster dose: 1%
1359
12.8% had history of SARS-CoV-2 infection
First dose: 3% pre-pregnancy, 14% during the first trimester, 51% during the second trimester, 32% during the third trimester None Anti-S IgG
Reported as relative index value
Anti-S IgG levels in fully vaccinated women by trimester of vaccination: 4.1 (pre-pregnancy), 4.2 (first trimester), 4.9 (second trimester), 6.2 (third trimester) Anti-S IgG levels in cord blood from fully vaccinated women by trimester of vaccination: 4.5 (pre-pregnancy); 4.7 (first trimester); 5.5 (second trimester); 6.3 (third trimester) Not shown Third trimester
vaccination associated with highest responses in maternal and cord blood
Ad26.COV2.S no difference in responses by trimester of vaccination and always lower than the mRNA vaccines
In women with history of SARS-CoV-2 infection, maternal and cord blood responses after vaccination in early pregnancy were comparable to third trimester vaccination in pregnant women without history of infection
Pylon 3D platform, ET HealthCare [55]
Poland
Dates not reported
Two doses
BNT162b2
16 First dose: 31.8 (±2.1) weeks GA
Second dose 35.1 (±2.1) weeks GA
From second dose to delivery 5.5 (±2.1) weeks
None Anti-RBD IgG
Reported as U/ml
100% positive
984.37 U/ml (±689.4)
100% positive
1026.51 U/ml (±769.25)
1.28 (±0.80) Cord blood and placental transfer ratio associated positively with time from first dose and second dose to delivery Elecsys Anti-SARS-CoV-2-S-RBD assay, Roche Diagnostics [57]
Romania
May–December 2021
BNT162b2
Ad26.CO
227 Third trimester 54 Pregnant women who had COVID-19
529 Non-pregnant vaccinated women, uninfected
Anti-RBD IgG
Reported as U/ml
Vaccinated group not previously infected – before vaccination: 0.41 (0.31–0.45); 1 month post-fully vaccinated: 2433 (1752–3094); 2 months post-fully vaccinated: 1697 (1393–2115); 3 months post-fully vaccinated: 1314 (1095–1762); 4 months post-fully vaccinated: 1083 (896–1468)
Vaccinated group previously infected – before vaccination: 145 (98.2–208.1); 1 month post-fully vaccinated: 15 360 (13 551–16 318); 2 months post-fully vaccinated: 14 571 (12 628–15 337); 3 months post-fully vaccinated: 12 870 (10 644–14 349); 4 months post-fully vaccinated: 10 759 (9043–12 571)
Non-pregnant group – before vaccination: 0.40 (0.32–0.47); 1 month post-fully vaccinated: 2461 (1719–3176); 2 months post-fully vaccinated: 1705 (1452–2179); 3 months post-fully vaccinated: 1377 (1147–1822); 4 months post-fully vaccinated: 1114 (909–1483)
Not shown Not shown Elecsys Anti-SARS-CoV-2-S-RBD assay, Roche Diagnostics [59]
a

Abbreviations: AU/ml, arbitrary units per milliliter; GA, gestational age; IQR, interquartile range; RBD, receptor-binding domain; S, spike protein; U/ml, units per milliliter.

b

Blood samples collected at delivery if not stated otherwise.