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Microbes & Immunity Homologous versus heterologous COVID-19 vaccines

Table 2. (Continued)
No References Country Study design Vaccine (dose) Median age Groups Number of Intervention Interval
(range) subjects between
doses
31 Intapiboon Thailand RCT BNT 0.3 mL, IM 39.9 (18 – 61) Group 1 30 CoronaVac/ Interval of
et al., 2021 (Sinovac) (heterologous) CoronaVac/BNT 1 and 2
nd
36
st
BNT 0.15 mL IM) Group 2 30 CoronaVac/ dose: 21 days.
rd
(heterologous) CoronaVac/BNT Interval of 3
dose: 73 days
BNT 0.06 mL, ID Group 3 31 CoronaVac/
(heterologous) CoronaVac/BNT
CoronaVac Group 4 30 CoronaVac/
(0.5 mL) (homologous) CoronaVac
Abbreviations: IQR: Interquartile range; RCT: Randomized controlled trial.
Table 3. Comparing immune response parameters heterologous Ad 26 COV 2/BNT vaccination also showed
obtained from homologous versus heterologous COVID‑19 higher frequency of spike T cells level compared to its
vaccination regime corresponding homologous vaccination group (347.5 –
152 SFC/10 PBMC). 20
6
Immune response Total Number of studies showing
parameters studies higher immune parameters 3.2.4. Neutralizing antibodies
with *heterologous
COVID‑19 vaccination The studies measured neutralizing antibody titers for
regime (n [%]) pseudo-type viruses and the SARS-CoV-2 variants of
Anti-spike IgG antibodies 24 19 (79) concern (VOC), including alpha, beta, delta, and the
Anti-Spike IgA antibodies 3 3 (100) Omicron variant. Overall, receiving a heterologous vaccine
Anti-receptor binding 10 8 (80) regimen produced higher neutralizing antibody titers
domain antibodies and had more potent neutralizing activity against VOC
T-cell responses 3 3 (100) compared to homologous vaccination (Table 4).
Note: *Heterologous: Different COVID-19 vaccines used in the first In the Com-COV study by Liu et al., heterologous
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and second vaccination schedules. ChAd/BNT vaccination revealed a higher neutralizing
antibody titer than homologous ChAd/ChAd (antibody
An observational study in Germany reported higher titer: 515 to 61) with a GMR of 8.5, demonstrating
anti-RBD/S1 antibody levels (P < 0.05) in a heterologous non-inferiority-of-heterologous-vaccination against
group (ChAd/BNT: 9,378.50 U/mL) compared to a homologous vaccination. In contrast, participants
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homologous group (ChAd/ChAd: 826.30 U/mL). 35 vaccinated with heterologous BNT/ChAd had lower
neutralizing antibodies compared to the group receiving
3.2.3. T-cell responses
homologous BNT/BNT (antibody titer: 383 to 574). In
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In general, the heterologous vaccinations demonstrated addition, two other studies reported higher neutralizing
greater T-cell response to the spike protein compared to antibodies, in terms of percentage of inhibition, for
homologous vaccinations (Table 3). A prospective cohort heterologous ChAd/BNT (96.80 – 100%) and homologous
study conducted in Germany by Hillus et al., demonstrated BNT/BNT (97 – 100%) compared to homologous ChAd/
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that participants vaccinated with heterologous ChAd/BNT ChAd (93.50 – 98%). 10,26 In the Com-COV 2 study,
had higher spike T-cells against the SARS-CoV-2 virus both heterologous ChAd/mRNA-1273 and ChAd/NVX
with a value of 4762 mIU/mL compared to homologous vaccinations were not inferior to homologous ChAd/
ChAd and homologous BNT vaccinations (1061 mIU/mL, ChAd, with a GMR of 10 and 3.4 while exhibiting
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2,026 mIU/mL, respectively). In the Com-COV and robust neutralizing antibody titers of 1358 and 473,
Com-COV 2 RCT, groups who received heterologous respectively. Likewise, heterologous vaccination with
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ChAd with BNT, mRNA-1273 or NVX all demonstrated BNT/mRNA-123 and BNT/NVX showed non-inferiority
spike T cells levels that were higher than homologous to homologous BNT/BNT vaccination with a GMR of
ChAd and homologous BNT vaccinations (ChAd/BNT: 1.4 and 0.9, respectively, with neutralizing antibody titers
184 SFC per million PBMC, ChAd/mRNA-1273: 148 SFC of 1260 and 787. A clinical trial conducted by Atmar
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per million PBMC, ChAd/NVX: 190 SFC per million et al. demonstrated that heterologous vaccination with
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PBMC). 22,28 Another study that observed the effect of Ad 26/mRNA-1273 and Ad 26/BNT showed higher

Volume 1 Issue 2 (2024) 23 doi: 10.36922/mi.3757