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Introduction Recombinant Newcastle Disease virus (rNDV) vectored vaccines are safe mucosal applicable vaccines with intrinsic immune‐modulatory properties for the induction of efficient immunity. Like all viral vectored vaccines repeated inoculation via mucosal routes invariably results to immunity against viral vaccine vectors. To obviate immunity against viral vaccine vectors and improve the ability of rNDV vectored vaccines in inducing T cell immunity in murine air way we have directed dendritic cell targeted HIV‐1 gag protein (DEC‐Gag) vaccine; for the induction of helper CD4+ T cells to a Recombinant Newcastle disease virus expressing codon optimized HIV‐1 Gag P55 (rNDV‐L‐Gag) vaccine. Methods We do so through successive administration of anti‐DEC205‐gagP24 protein plus polyICLC (DEC‐Gag) vaccine and rNDV‐L‐Gag. First strong gag specific helper CD4+ T cells are induced in mice by selected targeting of anti‐DEC205‐gagP24 protein vaccine to dendritic cells (DC) in situ together with polyICLC as adjuvant. This targeting helped T cell immunity develop to a subsequent rNDV‐L‐Gag vaccine and improved both systemic and mucosal gag specific immunity. Results This sequential DEC‐Gag vaccine prime followed by an rNDV‐L‐gag boost results to improved viral vectored immunization in murine airway, including mobilization of protective CD8+ T cells to a pathogenic virus infection site. Conclusion Thus, complementary prime boost vaccination, in which prime and boost favor distinct types of T cell immunity, improves viral vectored immunization, including mobilization of protective CD8+T cells to a pathogenic virus infection site such as the murine airway.

Introduction Targeting antigens to dendritic cells (DCs) in vivo via a DC-restricted endocytic receptor, DEC205, has been validated to enhance immunity in several vaccine platforms. Particularly atttractive is selected delivery of proteins to DCs in vivo because it enables proteins to be more immunogenic and provides a cheaper and effective way for repeated immunizations. Methods In this study, we tested the efficacy of a single chain antibody to DEC205 (scDEC) to deliver protein antigens selectively to DCs in vivo and to induce protective immunity. Results In comparison to soluble Ovalbumin (OVA) antigen, when recombinant scDEC:OVA protein was injected subcutaneously (s.c.) into mice, the OVA protein was selectively presented by DCs to both TCR transgenic CD8+ and CD4+ T cells approximately 500 and 100 times more efficient than soluble OVA, respectively, and could persist for seven days following s.c. injection of the scDEC205:OVA. Similarly selective targeting of HIV Gag P24 to DCs in vivo using scDEC-Gag protein plus polyICLC vaccine resulted in strong, long lasting, polyfuntional CD4+ T cells in mice which were protective against airway challenge by a recombinant vaccinia-gag virus. Conclusion Thus targeting protein antigens to DCs using scDEC can be used either alone or in combination with other strategies for effective immunization.

Immunoglobulin G specific responses againstPlasmodium falciparummerozoite antigens such as the merozoite surface protein 3 (MSP3) and UB05 are known to play critical roles in parasitemia control and protection from symptomatic illness. However when there is intense perennial malaria transmission coupled with concurrent infection with the human immunodeficiency virus type 1 (HIV), knowledge of IgG antibody response profiles is limited. In this study we assessed the impact of dual HIV-Malaria infections on IgG subclass responses to MSP3 (QβMSP3) and UB05 (QβUB05) in individuals living in two areas of Cameroon differing in transmission intensity. We observed differences in antigen specific IgG and IgG subclass responses which was dependent upon the antigen type, malaria transmission intensity, HIV infection, malaria infection and dual HIV-malaria infections. Individuals living in high malaria transmission areas irrespective of HIV or malaria status had significantly higher IgG responses to both antigens (P=0.0001 for QβMSP3, P=0.0001 for QβUB05) than their counterpart from low transmission areas. When dual HIV-Malaria infection is considered significantly higher QβMSP3 specific IgG1 (P=0.0001) and IgG3 (P=0.04) responses in double negative individuals was associated with protection against malaria in low transmission areas. Superior QβUBO5 specific IgG1 responses (P=0.0001) in double negative individuals were associated with protection in high transmission areas in contrast to significantly higher IgG3 responses to QβUB05 (P=0.0001) which were more relevant to protection in low malaria transmission areas in the same population. Thus, understanding immune responses to QβUB05 and QβMSP3 could facilitate the development of immunotherapeutic strategies suitable for areas differing in malaria transmission intensity.

Background In West and Central Africa areas of endemic Loa loa infections overlap with regions of high prevalence of human immunodeficiency virus type 1 (HIV-1) infections. Because individuals in this region are exposed to filarial parasites from birth, most HIV-1 infected individuals invariably also have a history of filarial parasite infection. Since HIV-1 infection both depletes immune system and maintains it in perpetual inflammation, this can hamper Loa loa filarial parasite mediated immune modulation, leading to enhanced loaisis. Methods In this study we have assessed in plasma from asymptomatic anti-retroviral (ARV) naïve Loa loa microfilaraemic HIV-1 infected people the filarial antibody responses specific to a filariasis composite antigen consisting of Wbgp29-BmR1-BmM14-WbSXP. The antibody responses specific to the filariasis composite antigen was determined by enzyme linked immunosorbent assay (ELISA) in plasma from ARV naïve Loa loa microfilaraemic HIV-1 infected participants. In addition the filarial antigen specific IgG antibody subclass profiles were also determined for both HIV-1 positive and negative people. Results Both Loa loa microfilaraemic HIV-1 positive and negative individuals showed significantly higher plasma levels of IgG1 (P