The 3-dose tetravalent HPV-16/18/33/58 vaccine

adjuvanted with AS01 induced higher levels of cross-reacting antibodies to non-vaccine antigens ABT-737 mouse (HPV-31, -45 and -52) one month after the last vaccine dose than vaccines adjuvanted with AS02 or AS04 (Supplementary Fig. 2). Cross-reacting antibody responses tended to be lower when the HPV-16/18/33/58 AS01 vaccine was administered on a 2-dose schedule than a 3-dose schedule. In TETRA-051 (Fig. 3A), all vaccines induced similar frequencies of HPV-16 and -18 specific memory B-cells one month after the last vaccine dose, but the frequencies of HPV-31 and -45 specific memory B-cells were higher in tetravalent HPV-16/18/31/45 vaccine groups than in the control group, regardless of VLP concentration (median HPV-31 specific B-cell counts per 106 B-cells [interquartile range] ranged from 2203 [1042–7567] to 5374 [2510–7642] for tetravalent formulations versus 263 [194–922] for control, and median HPV-45 specific B-cell counts ranged from 683 [437–2935] to 2246 see more [760–7538] for tetravalent formulations versus 198 [100–567] for control). In Study NG-001 (Fig. 3B), the median frequency of HPV-16 specific memory B-cells one month after the last vaccine dose was approximately 2-fold lower for the tetravalent

AS04 vaccine (729 [563–1484]) than control (1518 [865–2588]), whereas tetravalent vaccines adjuvanted with AS01 (4550 [2117–7031]) and AS02 (2950 [1384–5014]) induced higher median frequencies of HPV-16 specific B-cells than control. The median frequency of HPV-18 specific B-cells was approximately 1.6-fold lower for the tetravalent AS04 vaccine (512 [113–1312]) and

1.5-fold lower for the AS02 vaccine (533 [211–1139]) than control (818 [416–2134]), whereas the AS01 vaccine (919 [430–1493]) induced similar median frequencies of HPV-18 specific memory B-cells to control. The tetravalent formulations induced higher frequencies of HPV-33 and -58 specific B-cells, compared to cross-reacting HPV-33 and -58 specific B-cell responses induced by the control vaccine (HPV-33 specific B-cell counts ranged from 1453 [631–3044] to 5678 [2610–8551] for tetravalent formulations versus 124 [39–317] for control, and HPV-58 specific B-cell counts ranged secondly from 1907 [910–2452] to 4006 [2117–5805] for tetravalent formulations versus 112 [34–385] for control). Comparing the tetravalent formulations, the highest median B-cell response for all four vaccine types was induced by the AS01 formulation, regardless of dose schedule; the AS02 formulation induced an intermediate response and the AS04 formulation induced a lower response. In TETRA-051 (Fig. 4A), the control vaccine induced strong CD4+ T-cell responses to both HPV-16 and -18 one month following last vaccination, and induced cross-reacting CD4+ T-cell responses to HPV-31 and -45. All tetravalent formulations also induced high levels of CD4+ T-cells to HPV-16, -18, -31 and -45, regardless of VLP content. In Study NG-001 (Fig.