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Microbes & Immunity Homologous versus heterologous COVID-19 vaccines

2.3. Study selection the immunogenicity of heterologous vaccines against

The identified articles were imported into Endnote X9 homologous vaccines by measuring several parameters,
software to perform a primary duplicate screening. The namely, antibodies to the spike protein (IgG) of SARS-
remaining articles were then exported to Covidence CoV-2; antibodies to the RBD; neutralizing antibodies;
(https://www.covidence.org), an online software tailored and T-cell response to the spike protein. Immunological
for systematic reviews that facilitates de-duplication and data obtained from each study are summarized in Table 2.
screening. Articles were screened for eligibility based on 3.1. Characteristics of included studies
inclusion and exclusion criteria in a two-stage process:
(i) Title and abstract screening, followed by (ii) full-text The research methodology classified most of the identified
review. The inclusion criteria were original research studies as observational studies, with the remaining ones
articles from clinical trials or observational studies being clinical trials (Figure 2A). Geographically, more
comparing heterologous versus homologous COVID-19 than half of the studies were conducted in European
vaccination regimes, focusing on the immunogenicity countries such as Germany, the United Kingdom, Spain,
or efficacy of these regimes in healthy adults aged Italy, France, Denmark, and Sweden. Around one-third of
≥18 years old. Publications that were review articles the studies involve Asian continents such as China, Hong
(systematic, scoping, or narrative) or case reports articles, Kong, Thailand, Singapore, and India, while the remaining
examining only homologous COVID-19 vaccination, studies were done in the United States, Brazil, and Lebanon
studies involving subjects with pre-existing medical (Figure 2B).
conditions or pediatric populations, and animal studies A total of 128 vaccination strategies were reported in
were excluded using the search options of the database. the 31 short-listed research articles, which included 61
The screening process involved a total of three reviewers; heterologous vaccination groups (48%), 56 homologous
two researchers independently reviewed each paper, and vaccination groups (44%), and 11 control groups (8%)
any disagreements were resolved by the study supervisor. (Figure 3). Among the 61 heterologous vaccination
The Preferred Reporting Items for Systematic Reviews and strategies, the most popular combination investigated
Meta (PRISMA) chart was used to illustrate the screening was the AstraZeneca/Pfizer (ChAd/BNT) (13/61), where
and study selection process. subjects received the AstraZeneca (ChAd) as the first
vaccine, followed by the Pfizer (BNT) as the second vaccine
3. Results (Figure 4). Three studies used the AstraZeneca/Moderna
The literature search across the databases yielded 317 (ChAd/mRNA1273) combination; two studies used the
articles, which were imported into the Endnote X9 Pfizer/Moderna (BNT/mRNA1273) combination, while
software. Following an initial duplicate screening, 44 only one study used the Moderna/Pfizer (mRNA1273/
articles were identified as duplicates and removed. The BNT) combination (Figure 4).
remaining 273 articles were uploaded into Covidence, 3.2. Comparison of immune response parameters
where its de-duplication function identified and removed
an additional six duplicates, leaving 267 articles (Figure 1). The majority of the studies that compared homologous and
Following title and abstract screening, 175 articles were heterologous vaccination regimes reported higher anti-
excluded as irrelevant to the interest of this study. Among spike protein IgG and anti-spike protein IgA antibodies
the remaining 92 articles subjected to full-text review, (Table 3). Similar findings were observed with antibodies
65 articles were excluded for the following reasons: eight to the RBD and T-cell responses (Table 3).
studies were systematic reviews or case reports; two were
animal studies; four were irrelevant to this study; three 3.2.1. Antibodies to the spike protein
studies assessed the wrong outcomes; four studies involved In general, participants who received a heterologous
pediatric populations; two involved patient populations vaccine regimen exhibited a marked rise in spike IgG
with pre-existing medical conditions; 19 studies used wrong levels from baseline to 14 days after receiving the second
comparators; 17 studies had inappropriate interventions; dose booster and had higher titers compared to those
one study was an ongoing clinical trial; two studies were who received a homologous regimen. The Com-COV
study protocols; and three more were duplicates (Figure 1). study, a randomized controlled trial (RCT) conducted by
Ultimately, 27 articles met the inclusion criteria and Liu et al., revealed a higher spike in the IgG antibody
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were shortlisted for data extraction and analysis in this levels (P < 0.05) in the heterologous ChAd/BNT vaccine
scoping review. In addition, four studies were included group compared to the homologous ChAd/ChAd group
through a manual search on Google Scholar, totaling the with antibody levels of 12,906 EU/mL and 1,392 EU/mL,
included studies to 31 articles. These 31 studies compared respectively. The computed geometric mean ratio (GMR)

Volume 1 Issue 2 (2024) 14 doi: 10.36922/mi.3757