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Review
. 2017 Oct;16(10):973-985.
doi: 10.1080/14760584.2017.1371594. Epub 2017 Sep 4.

Immunogenicity and efficacy of DNA/MVA HIV vaccines in rhesus macaque models

Lynette Siv Chea  1 , Rama Rao Amara  1
Affiliations
Review

Immunogenicity and efficacy of DNA/MVA HIV vaccines in rhesus macaque models

Lynette Siv Chea et al. Expert Rev Vaccines. 2017 Oct.

Abstract

Despite 30 years of research on HIV, a vaccine to prevent infection and limit disease progression remains elusive. The RV144 trial showed moderate, but significant protection in humans and highlighted the contribution of antibody responses directed against HIV envelope as an important immune correlate for protection. Efforts to further build upon the progress include the use of a heterologous prime-boost regimen using DNA as the priming agent and the attenuated vaccinia virus, Modified Vaccinia Ankara (MVA), as a boosting vector for generating protective HIV-specific immunity. Areas covered: In this review, we summarize the immunogenicity of DNA/MVA vaccines in non-human primate models and describe the efficacy seen in SIV infection models. We discuss immunological correlates of protection determined by these studies and potential approaches for improving the protective immunity. Additionally, we describe the current progress of DNA/MVA vaccines in human trials. Expert commentary: Efforts over the past decade have provided the opportunity to better understand the dynamics of vaccine-induced immune responses and immune correlates of protection against HIV. Based on what we have learned, we outline multiple areas where the field will likely focus on in the next five years.

Keywords: AIDS; DNA; HIV vaccine; MVA; T cell responses; antibody responses; heterologous; modified vaccinia ankara; prime-boost.

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Figures

Figure 1.
Figure 1.. Schematics representing the patterns of vaccine-induced T cells and antibodies after DNA/MVA and MVA only immunizations in rhesus macaques.
Vaccine-induced responses after A) two DNA immunizations followed by two MVA immunizations or B) three MVA immunizations only [81,83]. Top row: SIV-specific CD8+ (blue) and CD4+ (orange) T cell responses. Env-specific serum IgG (purple) and IgA (green) levels in the serum (middle) or mucosae (bottom). Data for Env-specific serum IgA levels are not available for MVA only immunized animals. Please note that these graphs are only models to reveal the patterns and do not depict absolute values.
Figure 2.
Figure 2.. Schematic representation of VLPs expressing HIV antigens and CD40L activating Env-specific B cells and dendritic cells for cross-presentation.
Virus-like particles (VLPs) are produced to express trimeric Env and CD40L on the surface. A) VLPs activate B cells through interactions between Env and B cell receptors (BCR) as well as between CD40L and CD40 on B cells. CD40L mediated activation of B cells could promote affinity maturation, isotype switching, proliferation and survival leading to development of long lived memory B cells and plasma cells. B) CD40-CD40L interactions between VLPs and dendritic cells (DCs) leads to DC activation by upregulating T cell co-stimulatory molecules and cytokine production resulting in generation of long lived memory CD8 T cells [83]. Env expression on VLPs increases their targeting to DCs by binding to CD4.
Figure 3.
Figure 3.. Poxviruses express modulatory factors for cytokines, chemokines, and signaling pathways.
A poxvirus-infected cell is depicted here.
See this image and copyright information in PMC

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