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Microbes & Immunity Homologous versus heterologous COVID-19 vaccines

IgG, neutralizing antibodies, and spike T cells against the regimens generally elicit a strong immune response against
SARS-CoV-2 virus when compared to the homologous the SARS-CoV-2 virus in terms of spike IgG antibodies,
ChAd booster group. For the ChAd/ChAd/BNT group, RBD antibodies, neutralizing antibodies, and spike T
values were 20517 ELU/ml for spike IgG antibody levels, cells, compared to homologous vaccination regimens.
1621 for neutralizing antibodies, and 115.5 SFC per 10 Depending on the vaccine type, heterologous vaccination
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PBMC for spike T cells. The ChAd/ChAd/mRNA-1273 with a viral vector/mRNA vaccine, such as ChAd/BNT,
groups had values of 3,111 ELU/ml, 2,368 and 128.9 SFC exhibited robust immunogenicity, but when the order of
per 10 PBMC, respectively. For the other heterologous vaccines was reversed (mRNA/viral vector), the immune
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vaccine booster groups, including NVX, VLA, Ad 26, response was less potent. Similarly, heterologous regimens
and CVn, the spike IgG, spike T cells, and neutralizing that involve priming with an inactivated vaccine and
antibodies produced were generally higher compared to receiving a viral vector or mRNA vaccine boost, such as
the homologous ChAd booster group. On the other hand, CoronaVac/ChAd or CoronaVac/BNT, both demonstrated
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participants who were primed with 2 doses of BNT and strong immune responses, with the mRNA vaccine booster
received a heterologous NVX, VLA, or Ad 26 vaccine all being superior. Even heterologous regimens that involve
had lower immunogenicity in terms of spike IgG, spike BNT/mRNA-1273 seem to elicit a stronger humoral and
T-cell, and neutralizing antibody titers when compared to cellular response despite being produced by different
participants who received a homologous BNT booster. The companies and sharing the same vaccine platform. Similar
exception was seen in the heterologous BNT/BNT/mRNA- results were derived from an animal study that involved
1273 group that showed higher spike IgG, neutralizing heterologous vaccination of mice with an RNA vaccine and
antibodies, and spike T cells of 33,768 ELU/mL, 2,019, and a viral vector vaccine. The outcomes were strong cellular
112 SFC per 10 PBMC, respectively. A study conducted immunity and high neutralizing antibody titers, therefore
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in China by Ai et al., showed that heterologous vaccinated providing the prospect of implementing heterologous
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participants who had received two doses of an inactivated vaccination regimens in humans. 37
vaccine (BBIBP-CorV) and a protein subunit (Zifivax)
booster produced higher neutralizing antibodies against The underlying mechanism of heterologous vaccinations
SARS-CoV-2 VOC, including Beta, Delta, and Omicron, remains ambiguous; however, established evidence of the
with GMTs of 789.60, 1501, and 95.86, respectively, immunological mechanism of different vaccine types could
compared to the homologous BBIBP-CorV booster group explain this phenomenon. Firstly, mRNA vaccines can
(GMT of homologous group: Beta variant: 215.7, Delta: produce high titers of neutralizing and RBD antibodies but
250.8, Omicron: 48.73) at 14 days post booster vaccination. have lower CD8+ T cell response, while viral vector vaccines
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A similar finding was reported from a case-case study in produce potent T cell response and have polyfunctional
China where heterologous vaccination of BBIBP-CorV antibodies to mediate neutralizing antibodies. Inactivated
and CoronaVac displayed higher vaccine efficacy against vaccines, on the other hand, generally induce humoral
pneumonia and severe disease (79.5%) compared to the immunity and produce neutralizing antibodies. 38,39 This
homologous vaccination groups (CoronaVac: 61.8%; demonstrates that vaccines developed from different
BBIBP-CorV: 70.1%). 33 platforms provide protection against the SARS-CoV-2
Lastly, a study investigated the immunogenicity virus through divergent immunological pathways, and
of mRNA-based vaccines as boosters in subjects who therefore, receiving a heterologous vaccination would
previously received heterologous ChAd/BNT and allow benefits to be reaped from both sides.
homologous ChAd/ChAd vaccination. No significant Vaccine effectiveness and efficacy were demonstrated
difference was observed in anti-RBD/S1 antibody level in two studies. Gram et al. demonstrated the effectiveness
between ChAd/BNT/mRNA group and ChAd/ChAd/ of heterologous vaccination of ChAd and mRNA (BNT or
mRNA group (12,852 U/mL versus 10,582 U/mL). 35 mRNA-1273) vaccination (66 – 88%) to be higher than
a single dose of ChAd (−47 – 44%). Xu et al. reported
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4. Discussion superior vaccine efficacy against pneumonia and severe
The primary objective of this scoping review was to disease from heterologous vaccination of BBIBP-CorV
collate and summarize scientific evidence available and CoronaVac (79.5%) compared to the homologous
for heterologous and homologous vaccinations by vaccination cohorts (CoronaVac: 61.8%; BBIBP-CorV:
comparing their immunogenic profiles and discerning 70.1%). Regardless of the combination of vaccines
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if heterologous vaccinations provide better immunity administered, both studies have reported higher VE
against the SARS-CoV-2 virus. The evidence from the from heterologous vaccination compared to homologous
included studies showed that heterologous vaccination vaccination, supporting the deployment of a heterologous

Volume 1 Issue 2 (2024) 25 doi: 10.36922/mi.3757