Abstract
BackgroundAn 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.ResultsCo-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 co-immunisation 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.SignificanceThese 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.
Highlights
Development of an effective vaccine to prevent HIV-1 infection is critical to control the spread of HIV
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
Luminex analysis 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
Summary
Development of an effective vaccine to prevent HIV-1 infection is critical to control the spread of HIV. Data from the rhesus macaque model indicates that HIV-1 Env specific neutralizing antibodies protect against mucosal [1,2,3] and intravenous SHIV challenge [4, 5], as well as from heterologous SIV challenge [6] reducing the pathogenic effects of infection such as CD4 + T-cell loss, and the viral set-point [1, 4, 6]. Current data suggest that an effective vaccine will likely need to induce both cellular and humoral immune responses to reduce the rate of HIV-1 infection and control virus replication in the advent of breakthrough infection. 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.
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