Background
An effective HIV vaccine will likely require induction of both mucosal and systemic cellular
and humoral immune responses. We investigated whether intramuscular (IM) delivery of
electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal
(IN) and IM routes could be combined to induce mucosal and systemic cellular and humoral
immune responses to a model HIV-1 CN54 gp140 antigen in mice.
Results
Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal
IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic
or mucosal IgA responses. Cellular IFNγ responses were preserved in coimmunisation
protocols compared to protein-only vaccination groups. The addition of DNA
to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination
alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein
induced expression of cytokines that promote B-cell function, generation of TFH cells and
CCR5 ligands that can reduce HIV infectivity.
Significance
These data suggest that while IN inoculation alone elicits both cellular and humoral
responses, co-administration with homologous DNA vaccination can tailor these towards a
more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting
high-levels of antigen-specific antibody. This work provides insights on how to generate differential
immune responses within the same vaccination visit, and supports co-immunisation
with DNA and protein by a mucosal route as a potential delivery strategy for HIV
vaccines.