Abstract
ABSTRACTAn important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia virus Ankara (MVA) expressing HIV-1 Env on virus-like particles. In this study, we evaluated whether the addition of a gp120 protein in alum or MVA-expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime-MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26, and 40. Both boost immunogens enhanced the breadth of HIV-1 gp120 and V1V2 responses, antibody-dependent cellular cytotoxicity (ADCC), and low-titer tier 1B and tier 2 neutralizing antibody responses. However, there were differences in antibody kinetics, linear epitope specificity, and CD4 T cell responses between the groups. The gp120 protein boost elicited earlier and higher peak responses, whereas the MVAgp140 boost resulted in improved antibody durability and comparable peak responses after the final immunization. Linear V3 specific IgG responses were particularly enhanced by the gp120 boost, whereas the MVAgp140 boost also enhanced responses to linear C5 and C2.2 epitopes. Interestingly, gp120, but not the MVAgp140 boost, increased peak CD4+ T cell responses. Thus, both gp120 and MVAgp140 can augment potential protection of a DNA/MVA vaccine by enhancing gp120 and V1/V2 antibody responses, whereas potential protection by gp120, but not MVAgp140 boosts, may be further impacted by increased CD4+ T cell responses.IMPORTANCE Prior immune correlate analyses with humans and nonhuman primates revealed the importance of antibody responses in preventing HIV-1 infection. A DNA prime-modified vaccinia virus Ankara (MVA) boost vaccine has proven to be potent in eliciting antibody responses. Here we explore the ability of boosts with recombinant gp120 protein or MVA-expressed gp140 to enhance antibody responses elicited by the GOVX-B11 DNA prime-MVA boost vaccine. We found that both types of immunogen boosts enhanced potentially protective antibody responses, whereas the gp120 protein boosts also increased CD4+ T cell responses. Our data provide important information for HIV vaccine designs that aim for effective and balanced humoral and T cell responses.
Highlights
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity
We found that both types of immunogen boosts enhanced potentially protective antibody responses, whereas the gp120 protein boosts increased CD4ϩ T cell responses
Increasing the titers of antibodies to gp120 and, in particular, to the V1V2 region of gp120 is considered desirable because gp120 is the major target for neutralizing antibodies for HIV [2] and because binding antibodies for V1V2 were a correlate for reduced HIV-1 risk in the partially efficacious RV144 vaccine trial in Thailand [3, 4]
Summary
An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. GOVX-B11, a subtype B DNA prime-modified vaccinia virus Ankara (MVA) boost vaccine, elicits higher response rates and titers of antibodies to the gp transmembrane than the gp120 receptor binding subunit of Env [1]. Both components of GOVX-B11 express virus-like particles (VLPs) displaying membrane-bound Env. The current study was undertaken to test the ability of gp120 protein or MVA-expressed secreted gp140 (MVAgp140; the ectodomain of Env) to boost the ability of GOVX-B11 to elicit gp120 antibodies. We delivered the gp120 protein or MVAgp140 boosts to the contralateral arm from the MVA62B boosts and used our most successful clinical regimen for immunizations: priming with DNA at months 0 and 2 and boosting with MVA at months 4, 6, and 10 [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
