Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review

Lv, Jingjing; Wu, Hui; Xu, Junjie; Liu, Jiaye

doi:10.1186/s40249-022-00977-x

Table 1 Main characteristics of included studies and subjects

From: Immunogenicity and safety of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine: a systematic review

First author	Year	Country	Design	Vaccination schedule	Prime-boost interval (days)	N	Age (years)	Male (n,%)	Boost-outcomes interval	Outcomes
Louise Benning [21]	2021	Germany	Prospective cohort	ChAd/ChAd	82 (82–83)^a	17	55 (33–60)^a	6 (35)	20 (19–21)^a	Anti-S1 IgG, SARS-CoV-2 Neutralizing Antibodies, IgG antibodies against different SARS-CoV-2 target antigens
				ChAd/BNT	83 (77–84)^a	35	30 (24–45)^a	12 (34)	20 (19–21)^a
				BNT/BNT	20 (20–20)^a	82	45 (33–56)^a	19 (23)	20 (19–21)^a
Joana Barros-Martins [12]	2021	Germany	Retrospective cohort	ChAd/ChAd	73 (45–85)^a	32	41 (21–64)^a	12 (38)	16 (13–22)^a	Anti-S IgG, Anti-S IgA, Neutralizing Antibodies, frequency and phenotype of B cells and T cells
				ChAd/BNT	74 (62–84)^a	55	39 (22–61)^a	15 (27)	17 (13–23)^a
				BNT/BNT	22 (18–28)^a	21	38 (23–59)^a	9 (43)	30 (15–65)^a
Xinxue Liu [14]	2021	UK	RCT	ChAd/ChAd	28	90^c 25^d	57.6 (50.1–69.1)^ac 55.3 (50.7–64.1)^ad	52 (58)^c 12 (48)^d	28	Anti spike IgG, Normalised NT50(Live virus neutralising antibody), NT50(Pseudotype virus neutralising antibody), SFC per million PBMCs, Adverse events
				ChAd/BNT	28	90^c 24^d	57.6 (50.1–69.1)^ac 58.9 (51.8–68.3)^ad	50 (56)^c 15 (63)^d	28
				BNT/BNT	28	93^c 26^d	57.7 (50.2–69.3)^ac 54.7 (50.1–67.2)^ad	44 (47)^c 14 (54)^d	28
				BNT/ChAd	28	90^c 25^d	56.1 (50.5–68.9)^ac 55.8 (51.4–67.0)^ad	49 (54)^c 15 (60)^d	28
Alexandre Vallée [28]	2021	France	Retrospective, cross-sectional	ChAd/BNT	84 (3)^a	130	37 (13)^a	26 (20)	38 (7)^a	Anti spike IgG
				BNT/BNT	27 (6)^a	67	32 (11)^a	8 (12)	42 (9)^a	Anti spike IgG
Tina Schmidt [26]	2021	Germany	Cohort	ChAd/ChAd	10.8 ± 1.4week^b	55	48.6 ± 11.9^b	20 (36)	14 (2)^a	Spike-specific IgG, neutralizing antibody, spike-specific CD4 and CD9 T cells, B cells, Adverse events
				ChAd/BNT	11.2 ± 1.3week^b	97	40.8 ± 11.1^b	26 (27)	14 (1)^a
				BNT/BNT	4.3 ± 1.1weeks^b	64	44.7 ± 14.3^b	18 (28)	14 (1.25)^a
David Hillus [13]	2021	Germany	Prospective cohort	ChAd/ChAd	83 (71–84)^a	36^c 36^d	51 (33–59)^ac 51 (33–59)^ad	13 (36)^c 13 (36)^d	24 (20–28)^a	full spike-IgG, S1-IgG, RBD-IgG, neutralising antibody, IFN-γ
				ChAd/BNT	71 (70–73)^a	104^c 94^d	37 (29–51)^c 37 (29–48)^ad	26 (25)^c 23 (24)^d	21 (20–21)^a
				BNT/BNT	21 (21–21)^a	159^c 101^d	34 (29–43)^c 35 (30–47)^ad	72 (45)^c 28 (28)^d	28 (27–31)^a
Dorit Fabricius [15]	2021	Germany	Cohort	BNT/BNT	German guidelines	15	47 (26–64)^a	3 (20)	14 or 21^a	Neutralization capacities, anti-spike IgG titers, IFN-γ
				mRNA-1273/mRNA-1273	German guidelines	13	51 (34–61)^a	5 (38)	14 or 21^a
				ChAd/BNT	German guidelines	26	44 (22–64)^a	24 (92)	14 or 21^a
				ChAd/mRNA-1273	German guidelines	10	33 (21–47)^a	3 (30)	14 or 21^a
Matthias Tenbusch [27]	2021	Germany	Cohort	ChAd/BNT	63 (63–77)^a 63 (63–63)^a	232^e 250^e	47 (33–55)^ae 52 (31–59)^a	42 (18)^e 90 (36)^e	14 (13–15)^ad 14 (14)^ad	Surrogate neutralization activity
				BNT/BNT	21 (21–22)^a 23 (21–25)^a	410^e 127^e	38 (31–48)^ae 41 (27–52)^ae	162 (40)^e 37 (29)^e	14 (13–15)^ad 15 (13–15)^ad
				ChAd/ChAd	63 (63–63)^a	66^e	57 (45–62)^ae	23 (35) ^e	15 (13–15)^a
Swantje I. Hammerschmidt [23]	2021	Germany	Cohort	ChAd/ChAd	68 (45–91)^a	31	NR	11 (35)	17 (13–23)^a	Reciprocal titers of Neutralizing Antibodies
				ChAd/BNT	68 (45–91)^a	54	NR	14 (26)	17 (13–23)^a
				BNT/BNT	21 (18–27)^a	30	NR	9 (30)	30 (15–65)^a
Rudiger Gross [22]	2022	Germany	Retrospective cohort	ChAd/BNT	56^a	26	31 (25–46)^a	10 (38)	14–19^a	Anti-spike-IgM and IgG, surrogate virus neutralization, 50% pseudovirus neutralization, IFN-γ, IFN-α, IL-2
				BNT/BNT	21^a	14	42 (25–65)^a	10 (71)	13–15^a
Bruno Pozzetto [25]	2021	France	Cohort	ChAd/BNT	85 (84–85)^a	29	34 (27–40)^a	9 (31)	30 (28–34)^a	RBD and spike S1-specific IgG, IgA, neutralizing activity
				BNT/BNT	29 (26–31)^a	31	41 (33–52)^a	8 (26)	28 (27–31)^a	RBD and spike S1-specific IgG, IgA, neutralizing activity
Samantha J Westrop [29]	2022	UK	Contemporaneous cohort	ChAd/BNT	73 (64–83)^a	237	47 (37–59)^a	55 (23)	30 (21–39)^a	IgG antibody levels against the SARS-CoV-2 spike protein (S-antibody) and Nucleoprotein (N-antibody)
				BNT/BNT	76 (70–76)^a	135	71 (69–72)^a	64 (47)	30 (21–39)^a
				ChAd/ChAd	70 (54–77)^a	121	65 (54–69)^a	59 (49)	30 (21–39)^a
				BNT/ChAd	79 (65–99)^a	123	51 (40–63)^a	36 (29)	30 (21–39)^a
Swantje I. Hammerschmidt [24]	2022	Germany	Cohort	ChAd/mRNA-1273	80 (62–87)^a	42	38 (19–66)^a	13 (31)	14	Neutralizing antibodies against the Delta variant
				mRNA-1273/mRNA-1273	29 (27–42)^a	24	34 (23–63)^a	11 (44)	14
				ChAd/ChAd	78 (35–93)^a	38	47 (24–69)^a	15 (39)	14

Data in columns of “N”, “Age”, and “Male” represented the number of whole cohorts, we add special annotation (i.e. c, d, e) if data represented number of immunology cohorts or one study included more than one cohort
Ab antibody, BNT BNT162b2 vaccine, Pfizer–BioNTech, ChAd ChAdOx1 nCoV-19 vaccine, AstraZeneca, NR not reported, RBD receptor-binding domain, NT₅₀ 50% neutralising antibody titre, SFC spot-forming units, PBMC peripheral blood mononuclear cell, IFN-γ interferon-γ
^aData were presented as the median, median (Q1, Q3), or median (interquartile range)
^bData were presented as the mean ± standard deviation
^cData represented the number of whole cohorts
^dData presented the number of immunology cohorts
^eData presented the number of each cohort included in the study

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