Background: Naturally acquired immune responses to Plasmodium falciparum merozoite surface protein 3 (MSP3) and UB05 are implicated in semi immunity in populations living in malaria endemic areas. Thus designing chimeric malaria vaccine candidates involving MSP-3 and UB05 displayed upon the surface of a phage in its native form could potentiate their immunogenicity and antigenicity. In this study, we have engineered both MSP3 and UB05 upon the Qβ and assessed their antigenicity with plasma from children living in a high malaria transmission region of Cameroon. Methods: The surface of the RNA coliphage Qβ was genetically modified to display three Plasmodium falciparum derived immunogens including MSP3, UB05 and a chimera of the two UB05-MSP3. The resultant recombinant phages including QβMSP3, QβUB05 and QβUB05-MSP3 with surface displayed malaria immunogens were produced after transformation of the E. coli strain HB101. Plasma levels of antigen specific IgG antibody were then determined in samples from malaria positive and negative children living in a high malaria transmission region of Cameroon. Results: To improve yield each recombinant phage was scaled up to 10 14 pfu/ml using production strategies previously optimized in our group. This was significantly higher (P<0.001) relative to the 10 8 pfu/ml of the wild type C li nical M ic r o b io logy : O p e n Acces s

Regulatory T (Treg) cells play a key role in dampening excessive immune activation. However, antiretroviral therapy (ART) -naive HIV-1 infection maintains the immune system in a sustained state of activation that could alter both Treg cell surface markers and functions. As Treg cell surface markers are directly linked to their functions the overall objective of this study was to determine how ART-naive HIV infection affects the phenotypic properties of Treg cells. Our data showed that in ART-naive HIV-1 infection, Treg cells are dominated by effector (CD45RA CD27 CCR7 CD62L ) and effector memory (CD45RA CD27 CCR7 CD62L ) cells. In contrast Treg cells from HIV-negative individuals were mainly naive (CD45RA CD27 CCR7 CD62L ) and central memory (CD45RA CD27 CCR7 CD62L ) cells. Whereas effector and effector memory Treg cells showed enhanced expression of CD39 (P < 0·05), CD73 (P < 0·001), HLA-DR and CD38 (P < 0·001); naive and central memory Treg cells showed a significant reduction in the expression of these markers. Overall Treg cell frequencies within total CD4 T cells correlated positively with plasmatic HIV-1 viral load. As increased viral load is associated with augmented CD4 T-cell destruction; this could suggest a resistance of peripheral Treg cells to HIV-1 destruction. Hence the modulation of Treg cell phenotype and frequencies could be considered in designing immunotherapeutic strategies targeting immune system restoration during HIV-1 infection.

Thus targeting protein antigens to DCs using scDEC can be used either alone or in combination with other strategies for effective immunization.

IntroductionRecombinant 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.MethodsWe 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.ResultsThis 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.ConclusionThus, 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.

BackgroundIn 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.MethodsIn 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.ResultsBoth Loa loa microfilaraemic HIV-1 positive and negative individuals showed significantly higher plasma levels of IgG1 (P < 0.0001), IgG2 (P < 0.0001) and IgM (P < 0.0001) relative to amicrofilaraemic participants. A significant increase in IgE (P < 0.0001) was observed exclusively in Loa loa microfilaraemic HIV-1 infected people. In contrast there was a significant reduction in the level of IgG4 (p < 0.0001) and IgG3 (P < 0.0001) in Loa loa microfilaraemic HIV-1 infected individuals.ConclusionsLoa loa microfilaraemia in ARV naïve HIV-1 infected people through differential reduction of plasma levels of filarial antigen specific IgG3, IgG4 and a significant increase in plasma levels of filarial antigen specific IgE could diminish Loa loa mediated immune-regulation. This in effect can result to increase loaisis mediated immunopathology in antiretroviral naive HIV-1 infected people.

Background: In sub-Saharan Africa, intense perennial Plasmodium species transmission coincides with areas of high prevalence of the human immunodeficiency virus type 1 (HIV) infection. This implies that antiretroviral naïve HIV-infected people living within these regions

BackgroundDue to its unique challenge of establishing lifelong reservoirs a successful HIV-1 vaccine must elicit protective antibodies responses at the portals of entry. Broadly neutralising antibodies (bnAb) have been demonstrated not only to be therapeutic through suppressing viraemia in HIV-1 infected people but also preventive in blocking HIV-1 infection in animal models. This implies that a desirable HIV-1 vaccine candidate should be able to induce HIV-1 specific bnAb with an extensive ability to neutralise a broad range of HIV-1 isolates. Although several bnAb are known to target conserved regions in the HIV-1 envelope glycoprotein, no vaccination strategy has successfully produced such antibodies. Thus, the ability to optimise and deliver HIV envelope immunogens that can induce bnAb has remained a formidable challenge.MethodsTo optimise immunogens for inducing bnAb, our group has pursued two main directions. In the first instance we developed B cell immunogens mimicking the native HIV-1 enveloped gp120 glycoprotein. Supernatants of stably transfected mutant lec1 CHO cells using a flag tag. We next assess antibodies isotypes specific to this immunogen in plasma obtained from antiretroviral naive participants. Secondly, through surface engineering of the evolutionary phage Qbeta we built in several epitopes of bnAbs for effective delivery to the immune system. We next assess in plasma from 648 seropositive participants the abundance of antibody isotypes specific to these B cell immunogens.ResultsThe results obtained showed that all IgG isotypes were detected for both the manosylated and CHO wild-type expressed gp120. Although all IgG antibody isotypes including IgG1, IgG2, IgG3 and IgG4 were dictated, there was no significant difference between antibody titres directed to manosylated gp120 and wild-type gp120. Well over 87% of seropositive participants showed specific antibody responses to conserved B cell epitopes displayed on the surface of Qbeta phage.ConclusionsThese novel immunogens can be used as vaccine candidates.