Recombinant parvovirus-like particles as an antigen carrier: A novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells

151

Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8+ T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-αβ, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system.

Section: Ppv Vlpsmentioning

confidence: 99%

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Hervás-Stubbs

Rueda

López

et al. 2007

151

“…This pathway may be exploited for the development of nonreplicating, safe vaccines that nevertheless induce strong CTL responses. A variety of exogenous Ags have been shown to induce effective CTL responses in vivo, including Ags associated with apoptotic cells (10,11), cell debris (7,12,13), heat shock proteins (14), Sephadex beads (5), and virus-like particles (VLPs) (6,(15)(16)(17).…”

Section: Ajor Histocompatibility Complex Class I-and Mhcmentioning

confidence: 99%

Critical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles

Storni¹,

Lechner²,

Erdmann³

et al. 2002

113

111

Virus-like particles (VLPs) are known to induce strong Ab responses in the absence of adjuvants. In addition, VLPs are able to prime CTL responses in vivo. To study the efficiency of this latter process, we fused peptide p33 derived from lymphocytic choriomeningitis virus to the hepatitis B core Ag, which spontaneously assembles into VLPs (p33-VLPs). These p33-VLPs were efficiently processed in vitro and in vivo for MHC class I presentation. Nevertheless, p33-VLPs induced weak CTL responses that failed to mediate effective protection from viral challenge. However, if APCs were activated concomitantly in vivo using either anti-CD40 Abs or CpG oligonucleotides, the CTL responses induced were fully protective against infection with lymphocytic choriomeningitis virus or recombinant vaccinia virus. Moreover, these CTL responses were comparable to responses generally induced by live vaccines, because they could be measured in primary ex vivo 51Cr release assays. Thus, while VLPs alone are inefficient at inducing CTL responses, they become very powerful vaccines if applied together with substances that activate APCs.

“…VLPs have also been proven to be potent CTL inducers compared with other vectors (21)(22)(23)(24). A study of PPV-VLPs immunization showed a safe and efficient strategy to induce CTLs and stimulate antiviral immunity in a CD4-independent manner (22).…”

Section: O Ne Of the Major Effects During The Course Of Hiv Infectionmentioning

confidence: 99%

Th Cell-Independent Immune Responses to Chimeric Hemagglutinin/Simian Human Immunodeficiency Virus-Like Particles Vaccine

Yao

Zhang

Guo

et al. 2004

CD4+ Th cells are believed to be essential for the induction of humoral and cellular immune responses. In this study we tested the effect and possible mechanisms of the major antigenic component in influenza, hemagglutinin (HA), in helping HIV Env to induce immune responses in CD4+ T cell knockout (CD4 KO) mice. Simian HIV virus-like particles (SHIV VLPs) or phenotypically mixed chimeric influenza HA/SHIV VLPs were used as immunogens to immunize CD4 KO mice either i.p. or intranasally (i.n.). We found that chimeric HA/SHIV VLPs significantly induced a greater IgG Ab response in both i.p. and i.n. immunized mice and a greater IgA Ab response in mucosal washes in i.n. immunized mice compared with SHIV VLPs. Importantly, chimeric HA/SHIV VLPs induced ∼3-fold higher neutralizing Ab titers against HIV 89.6 than SHIV VLPs in the absence of CD4+ T cell help. There was also ∼40% more specific lysis of the HIV Env-expressing target cells in chimeric HA/SHIV VLP-immunized than in SHIV VLP-immunized CD4 KO mouse splenocytes. Moreover, we have found that chimeric HA/SHIV VLPs could efficiently bind and activate dendritic cells and stimulate the activated dendritic cells to secret TNF-α and IFN-γ. Therefore, chimeric HA/SHIV VLPs could efficiently prime and activate APCs, which could, in turn, induce immune responses in a CD4+ T cell-independent manner. This study suggests a novel adjuvant role of influenza HA as well as a new strategy to develop more effective therapeutic vaccines for AIDS patients with low CD4+ T cell counts.