Page 23 - JCTR-11-3

Journal of Clinical and
Translational Research Immunogenicity and safety of flu vaccines

subgroup analysis of adverse event types by comparing 3.3. Immunogenicity
the occurrence rates of different types of adverse events We conducted a systematic analysis of the GMTs,
between subunit IVs and split IVs. The heterogeneity of seroprotection rate, and seroconversion rate within
the outcomes was assessed utilizing the Chi-square test 20 – 30 days after influenza vaccination. Among them,
with the statistical significance threshold established at 18 studies reported results for seroprotection rate,
α = 0.05. If I > 50%, it indicates significant heterogeneity. 17 studies reported results for seroconversion, and
2
When significant heterogeneity exists, a random-effects 18 studies reported results for GMTs. We conducted
model based on the Mantel-Haenszel method would be subgroup analyses on three different types of IVs, including
used to estimate the overall effect size. If no significant subunit vaccines with adjuvant, non-adjuvanted subunit
heterogeneity could be observed (I ≤ 50%), the data would vaccines, and split vaccines.
2
be synthesized using the fixed-effects model.
3.3.1. Seroprotection
3. Results
We compared the seroprotection rates among different
3.1. Yield of search strategy vaccine groups targeting four different influenza viruses
The preliminary search of the database generated 10657 (A/H1N1, A/H3N2, B/Victoria [BV], and B/Yamagata
studies. After screening the titles and abstracts, 735 studies [BY]). According to the results in Figure 2, we found
were selected for whole-manuscript review. According to that these three types of vaccines displayed relatively
the inclusion and exclusion criteria, a total of 24 studies good seroprotection rates against the four influenza
that met the standard were finally included. These studies strains. Particularly, for the two influenza A strains,
would then be subjected to subsequent data examination H1N1 and H3N2, the seroprotection rates were both
and result integration. above 90% (H1N1: 94.99%, 95% confidence interval
[CI]: 93.38 – 96.59%, I = 96.40%; H3N2: 98.64%, 95%
2
3.2. Characteristics of included studies CI: 98.15 – 99.13%; I = 81.1%). As for the influenza
2
The included studies in this research encompassed B strains, the seroprotection rates also exceeded 80%
2
17 countries and regions globally. A total of 48,943 (BY: 89.93%, 95% CI: 86.32 – 92.53; I = 97.6%; BV: 83.49%,
2
participants was assessed in the immunogenicity and 95% CI: 78.58 – 88.41, I = 99.3%). Furthermore, the overall
seroprotection rate of the non-adjuvanted subunit IV was
safety analyses. The vaccines examined in these studies similar to that of the adjuvanted subunit IV and the split IV
included subunit IVs with adjuvant, subunit IVs without across the four influenza strains.
adjuvant, split IVs, and others. Among them, there
were nine studies comparing subunit vaccines with split 3.3.2. Seroconversion
vaccines, four studies comparing subunit vaccines with
or without adjuvant, four studies comparing subunit We further compared the seroconversion rates of
different vaccine groups against the four influenza strains,
vaccines produced in eggs versus cell culture, and the 20 – 30 days post-vaccination. As displayed in Figure 3,
remaining studies focusing on various other aspects the adjuvanted subunit IV exhibited significant superiority
of subunit IVs. Safety monitoring of the vaccinated over the other two IVs for H1N1 and BY strains with
population was conducted in 23 studies. In all included seroconversion rates of 87.05% and 83.04%, respectively.
studies, the route of vaccination was intramuscular As for H3N2, both the adjuvanted subunit IV and the
injection. More detailed information about each study is split IV demonstrated seroconversion rates above 80%,
summarized in Table 1.
outperforming the non-adjuvanted subunit IV. However,
Most of the selected studies were evaluated as small regarding the BV strain, the seroconversion rate of the
likelihood of unfairness. Only a few studies did not adjuvanted subunit IV was 65.69%, which was slightly
specify the assignment method and were classified lower than that of the non-adjuvanted and split IVs at
as ambiguous or at high risk of bias in the “selection 70.31% and 74.81%, respectively.
bias” category. Since our detection results are not
easily influenced by the blinding deficiency, the risks of 3.3.3. GMT
“performance bias” and “detection bias” in this study are We further compared the GMTs of different vaccine
assessed as low. In addition, some studies were evaluated groups against the four influenza strains, 20 – 30 days
as having “attrition bias” due to participant loss. The post-vaccination. Figure 4 illustrates the GMTs of
quality appraisal of individual studies is available in S3. different vaccine groups for different influenza strains.
Quality assessment of the included studies (Table S1) is For H1N1, the GMTs were 555.37 (448.38 – 666.36) for
provided in the Supplementary File. the adjuvanted subunit IV, 438.61 (340.77 – 536.45) for

Volume 11 Issue 3 (2025) 17 doi: 10.36922/JCTR025060006