Page 25 - JCTR-11-3

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

the non-adjuvanted IV, and 365.51 (257.96 – 473.07) for
References 44 45 46 13 the split IV. Notably, the GMTs of the two subunit IVs
were higher than that of the split vaccine. For H3N2, the
adjuvanted subunit IV and the split IV demonstrated
Type of virus strain IIV4 IIV3 IIV3 IIV4 higher GMTs. For the influenza B strains, the GMTs of the
non-adjuvanted subunit vaccine and the split vaccine were
similar but significantly lower than that of the adjuvanted
HA per strain (μg/dose) 15 15 15 7.5, 15 subunit vaccine. Overall, the adjuvanted subunit IV
provided the highest GMTs, while the non-adjuvanted
subunit IV and the split IV displayed similar GMTs.

3.4. Safety
Adjuvant An aggregate of 23 studies have documented the outcomes

None None None MF59 of side effects in relation to the administration of
subunit IVs and split IVs. To compare the safety profiles
of these two vaccine types, we extracted the most often
Duration 2018 – 2019 2013 – 2014 2013 – 2014 2016 – 2017 reported local and systemic adverse events from the

study data. A comprehensive statistical analysis was then
conducted to assess and compare the safety profiles of
these vaccine types.
4 – 20 years 4 – 17 years 3 – 18 years 7 years of adverse events was compared between subunit IVs
Age 12 months – According to the forest plot in Table 2, the incidence

(with adjuvant/without adjuvant) and split IVs. In the
Number of participants 171 2,055 430 1,601 comparison between non-adjuvanted subunit IV and split
vaccine, there was no remarkable difference in the total
adverse events (relative risk [RR]: 1.04, 95% CI: 0.94–1.16,
2
I = 0%, p=0.917), but the sample size was limited, and
Vaccine produced in Cell Cell/egg Cell/egg Egg further clinical studies are warranted for validation. In
the comparison between adjuvanted subunit IV and split
IV, the total adverse events were significantly higher for
adjuvanted subunit IV compared to the split IV (RR: 1.42,
95% CI: 1.32 – 1.52, I = 86.5%, p<0.001). It should also
2
be noted that none of the studies reported any cases of
USA, Australia, New Zealand, Philippines, Thailand Finland, Philippines, Thailand Abbreviations: IIV4: Quadrivalent inactivated influenza vaccine; IIV3: Trivalent inactivated influenza vaccine. impact of adjuvant use on the safety of subunit IVs.
Country mortality. Furthermore, the severity of adverse events was
not taken into consideration in the analysis.
Further comparison was conducted regarding the

adverse events across two vaccine groups (with or without
USA Spain, Italy Figure 5 presents the forest plot of the occurrence rate of
adjuvant). The results indicate that the total adverse
Study design Prospective Prospective Prospective Prospective event was significantly higher for the group receiving
adjuvanted subunit IV compared to the group receiving
non-adjuvanted subunit IV (RR: 1.54, 95% CI: 1.30 – 1.82,
I = 91.20%, p<0.001). This trend was also observed for
2
both local adverse events (RR: 1.35, 95% CI: 1.20 – 1.51,
Table 1. (Continued) Year First author 2020 Moehling et al. 2016 Nolan et al. 2016 Diez-Domingo et al. 2015 NCT02255409 I = 62.3%, p=0.021) and systemic adverse events (RR: 1.39,
2
95% CI: 1.19 – 1.62, I = 74.80%, p=0.001). Combining all
2
the included studies, the occurrence rate of side effects
was consistently higher for the group receiving adjuvanted
subunit IV compared to the group receiving non-adjuvanted

Volume 11 Issue 3 (2025) 19 subunit IV. doi: 10.36922/JCTR025060006