The RV144 HIV-1 vaccine trial results showed moderate reduction in viral 
infections among vaccinees as well as induction of antibody-dependent cellular 
cytotoxicity and vaccine-specific IgG and IgG3 responses directed at variable 
loop regions 1 and 2 of the HIV envelope protein. However, with the recent 
failure of the HVTN 702 clinical trial, comprehensive profiling of humoral 
immune responses may provide insight for these disappointing results. One of the 
changes included in the HVTN 702 study was the addition of a late boost, aimed 
at augmenting peak immunity and durability. The companion vaccine trial RV305 
was designed to permit the evaluation of the immunologic impact of late boosting 
with either the boosting protein antigen alone, the canarypox viral vector ALVAC 
alone, or a combination of both. Although previous data showed elevated levels 
of IgG antibodies in both boosting arms, regardless of ALVAC-HIV vector 
incorporation, the effect on shaping antibody effector function remains unclear. 
Thus, here we analyzed the antibody and functional profile induced by RV305 
boosting regimens and found that although IgG1 levels increased in both arms 
that included protein boosting, IgG3 levels were reduced compared with the 
original RV144 vaccine strategy. Most functional responses increased upon 
protein boosting, regardless of the viral vector-priming agent incorporation. 
These data suggest that the addition of a late protein boost alone is sufficient 
to increase functionally potent vaccine-specific antibodies previously 
associated with reduced risk of infection with HIV.