Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D.
Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.
Abbink
Peter
P
Research East Room 213, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Lemckert
Angelique A C
AA
Ewald
Bonnie A
BA
Lynch
Diana M
DM
Denholtz
Matthew
M
Smits
Shirley
S
Holterman
Lennart
L
Damen
Irma
I
Vogels
Ronald
R
Thorner
Anna R
AR
O'Brien
Kara L
KL
Carville
Angela
A
Mansfield
Keith G
KG
Goudsmit
Jaap
J
Havenga
Menzo J E
MJ
Barouch
Dan H
DH
D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000097:blood / Q000453:epidemiology*; D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017422:Sequence Analysis, DNA; D016036:Seroepidemiologic Studies; D012703:Serotyping; D014614:Vaccines, Synthetic / Q000235:genetics*; D014765:Viral Vaccines / Q000235:genetics*
D017931:DNA Primers; D014614:Vaccines, Synthetic; D014765:Viral Vaccines