. 2020 May 19;11:909. doi: 10.3389/fimmu.2020.00909

Table 2.

Summary of the comparative immunogenicity of diverse AdV vaccines.

A. Ad vectors compared	B. Vaccine antigen	C. Parameters used to define hierarchy of immunogenicity	Optimal vector	PMID
SPECIES: MICE
Human Ads B: Ad34, Ad35 C: Ad5, Ad6 D: Ad24 Non-human Ads B: ChAd30 C: ChAd3, PanAd3, PanAd1, PanAd2, ChAd11, ChAd19, ChAd20, ChAd24, ChAd31 (listed in order of immunogenicity) E: ChAd63, ChAd83, ChAd6, ChAd9, ChAd10, ChAd43, ChAd55, ChAd147, ChAd4, ChAd5, ChAd7, ChAd16, ChAd38, ChAd146, ChAd149, ChAd150 (listed in order of immunogenicity)	HIV-1 gag	Maintenance of Gag⁺CD8⁺IFNγ⁺ responses with dose de-escalation (10¹⁰-10⁶ vp): Ad5, Ad6 > Ad24 > Ad35 > Ad34 (Balb/c mice, intramuscular immunization) • Ad5 and Ad6 were capable of eliciting T cell responses at a vaccine dose of 10⁶ viral particles (vp). Ad24 = 10⁸ vp, Ad35 = 10⁹ vp, and Ad34 = 10¹⁰ vp. Maintenance of Gag⁺CD8⁺IFNγ⁺ responses with dose de-escalation (10¹⁰-10⁶ vp): ChAd3, PanAd3 > ChAd63 > PanAd1 > as listed in column A (Balb/c mice, intramuscular immunization) • 26 chimpanzee adenoviral isolates were screened for immunological potency. • Group C Ad vectors were most potently immunogenic, followed by Group E. Group B ChAd30 was weakly immunogenic. • ChAd3 and PanAd3 were capable of eliciting T cell responses at a dose of 10⁶ viral particles (vp), ranking them as comparable with the immunogenicity of Ad5. • ChAd63 also elicited T cell responses at 3 × 10⁶ vp making it only slightly less immunogenic than ChAd3 and PanAd3.	Ad5, Ad6 ChAd3, PanAd3, ChAd63	22218691
Human Ads B: Ad35 C: Ad5 D: Ad28 Non-human Ads C: ChAd3 E: ChAd63 ND: SAd11, SAd16	SIV gag	Magnitude and protective efficacy of CD8⁺ with dose de-escalation (10⁹-10⁷ particle units PU): Efficacy ranking: Ad5+ChAd3 > Ad28+SAd11 > ChAd63 > SAd16 > Ad35 (C57BL/6 mice, sub-cutaneous immunization) • Study performed a dose titration of vaccines with detailed phenotyping of T cell response at peak and memory timepoints. • Ad5, Ad28, SAd11, and ChAd3 were comparable in conferring CD8⁺ mediated protection in challenge model using gag-expressing Listeria monocytogenes.	Ad5, Ad28 ChAd3 SAd11	23390298
Human Ads B: Ad35 C: Ad5 D: Ad28 Non-human Ads C: ChAd3 E: ChAd63 ND: SAd11, SAd16	SIV gag eGFP	Memory (D70) Gag Tetramer⁺CD8⁺ at 10⁸ PU and protection from challenge: Ad5, ChAd3 > ChAd63 (C57BL/6 mice, sub-cutaneous immunization) • The protective efficacy of Ad vectors in a murine challenge model of gag-expressing Listeria monocytogenes was tested. • Ad5 and ChAd3 were most potently protective, followed by ChAd63. • Vaccination with Ads expressing reporter eGFP resulted in higher frequencies of eGFP⁺ CD11c⁺ dendritic cells in draining lymph nodes (dLNs) for Ad5, ChAd3 > ChAd63. • Transcriptional profiling of dLNs revealed that the most potently protective vectors, Ad5 and ChAd3, exhibited weak induction of IFN-stimulated genes, unlike other Ad vectors (8–24 h). • More pronounced upregulation of IFN-responsive gene modules in dLNs at 24 h were associated with reducing Ad transgene expression levels and thereby limiting their immunological potency.	Ad5 ChAd3, ChAd63	25642773
Human Ads B: Ad11, Ad35, Ad50 C: Ad5 D: Ad26, Ad48, Ad49	SIV gag	Maintenance of Gag⁺CD8⁺IFNγ⁺ responses with dose de-escalation (10¹⁰-10⁷ vp): Ad5 > Ad26 (C57BL/6 mice, intramuscular immunization) • A head-to-head comparison of species B and D Ad-based vaccine vectors was performed compared with species C Ad5. • At a dose of 10⁷ vp, Ad5 and Ad26 were more potent than all other Ad vectors, but only Ad5 was immunogenic at a dose of 10⁶ vp.	Ad5, Ad26	17329340
Human Ads C: Ad5 D: Ad26 Non-human Ads E: AdC6 (SAdV-23), AdC7 (SAdV-24)	HIV-1 gag Rabies glycoprotein	Magnitude of Gag⁺CD8⁺IFNγ⁺ responses at 10⁹ or 10⁸ vp: Ad5 > Ad26, AdC6, AdC7 (Balb/c mice, intramuscular immunization) • At 10¹⁰ vp gag-specific CD8+ responses were comparable for Ad5, Ad26, AdC6, and AdC7. • At 10⁸ vp, Ad5 was superior to all. Induction of NAbs to Rabies GP and Protective Efficacy at 10¹¹-10⁹ vp: Ad5 > Ad26, AdC6, AdC7 (ICR outbred mice, intramuscular immunization) • At all doses neutralizing antibodies considered protective according to comparison with WHO standard serum samples (>0.5 IU) were induced, but Ad5 was the best. • Ad5 had superior protective efficacy from challenge with rabies virus strain CVS-24 at all doses, survival with other Ads was reduced, even at 10¹¹ vp. • Ad26 displayed 60% survival, AdC6 was ~50% survival at 10¹¹ vp.	Ad5, Ad26 Ad26, AdC6	20686035

We are only including murine studies that performed a head-to-head comparison of vector immunogenicity for Ad vaccines derived from more than three Ad species groups. Please note, vector type names are listed as shortened versions due to space constraints within the Table. IFNγ, interferon gamma; vp, viral particle; PU, particle unit; HIV, human immunodeficiency virus; SIV, simian immunodeficiency virus; eGFP, enhanced green fluorescent protein; dLN, draining lymph node; GP, glycoprotein. Abbreviated “alternative” names for Ad vectors are used in this table due to space constraints. See Table 1 for their standardized nomenclature.