Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine Microbial Immunity and Vaccines

In this study, we further assessed the Plasmodium falciparum antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. We previously demonstrated that this regimen could provide partial protection against challenge with chimeric P. berghei parasites expressing PfUIS3. We now show that ChAd63-MVA PfUIS3 can also provide partial cross-species protection against challenge with wild-type P. berghei parasites. We also show that PfUIS3-specific cellular memory responses could be recalled in human volunteers exposed to P. falciparum parasites in a controlled human malaria infection study. When ChAd63-MVA PfUIS3 was coadministered with the vaccine candidate P. falciparum thrombospondin-related adhesion protein (PfTRAP) expressed in the ChAd63-MVA system, there was no significant change in immunogenicity to either vaccine. However, when mice were challenged with double chimeric P. berghei-P. falciparum parasites expressing both PfUIS3 and PfTRAP, vaccine efficacy was improved to 100% sterile protection. This synergistic effect was evident only when the two vaccines were mixed and administered at the same site. We have therefore demonstrated that vaccination with PfUIS3 can induce a consistent delay in patent parasitemia across mouse strains and against chimeric parasites expressing PfUIS3 as well ...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Microbial Immunity and Vaccines Source Type: research

Related Links:

Malaria parasites undergo several stages in their complex lifecycle. To achieve reductions in both the individual disease burden and malaria transmission within communities, a multi-stage malaria vaccine with high effectiveness and durability is a more efficacious strategy compared with a single-stage vaccine. Here, we generated viral-vectored vaccines based on human adenovirus type 5 (AdHu5) and adeno-associated virus serotype 1 (AAV1) expressing a fusion protein of the pre-erythrocytic stage Plasmodium falciparum circumsporozoite protein (PfCSP) and the transmission-blocking sexual stage P25 protein (Pfs25). A two-dose h...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We examined immunity elicited by these vaccines in the context of two adjuvants approved for human use (AddaVax and Matrix-M). Matrix-M supported the highest anti-PvCSP antibody titers when combined with Rv21, and, interestingly, mixing PvCSP Rv21 and PvTRAP viral vectors enhanced immunity to malaria over levels provided by single vaccines.
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Microbial Immunity and Vaccines Source Type: research
LITFL • Life in the Fast Lane Medical Blog LITFL • Life in the Fast Lane Medical Blog - Emergency medicine and critical care medical education blog aka Tropical Travel Trouble 010 Peer Reviewer: Dr Jennifer Ho, ID physician QLD, Australia You are an ED doc working in Perth over schoolies week. An 18 yo man comes into ED complaining of fever, rash a “cracking headache” and body aches. He has just hopped off the plane from Bali where he spent the last 2 weeks partying, boozing and running amok. He got bitten by “loads” of mosquitoes because he forgot to take insect repellent. On e...
Source: Life in the Fast Lane - Category: Emergency Medicine Authors: Tags: Clinical Cases Tropical Medicine arthralgia dengue fever rash Source Type: blogs
LITFL • Life in the Fast Lane Medical Blog LITFL • Life in the Fast Lane Medical Blog - Emergency medicine and critical care medical education blog aka Tropical Travel Trouble 009 The diagnosis of HIV is no longer fatal and the term AIDS is becoming less frequent. In many countries, people with HIV are living longer than those with diabetes. This post will hopefully teach the basics of a complex disease and demystify some of the potential diseases you need to consider in those who are severely immunosuppressed. While trying to be comprehensive this post can not be exhaustive (as you can imagine any patient with ...
Source: Life in the Fast Lane - Category: Emergency Medicine Authors: Tags: Clinical Cases Tropical Medicine AIDS art cryptococcoma cryptococcus HIV HIV1 HIV2 PEP PrEP TB toxoplasma tuberculoma Source Type: blogs
Abstract Adenovirus (Ad) is thought to be one of the most promising platforms for a malaria vaccine targeted against its liver stages, because of its ability to induce a strong T-cell response against a transgene. However, a further improvement of this platform is needed in order to elicit another arm of the immunity, i.e. humoral response, against malaria. In order to augment immunogenicity and protective efficacy of Ad-based malaria vaccine, we inserted B-cell, as well as CD4+ T-cell, epitopes of Plasmodium falciparum circumsporozoite protein (PfCSP) into the capsid protein, Hexon, and the core protein, VII (pVI...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Abstract Malaria remains a considerable burden on public health. In 2015, the WHO estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. A highly effective malaria vaccine is needed to reduce the burden of this disease. We have developed an experimental vaccine candidate (PyCMP) based on pre-erythrocytic (CSP) and erythrocytic (MSP1) stage antigens derived from the rodent malaria parasite P. yoelii. Our protein-based vaccine construct induces protective antibodies and CD4(+) T cell responses. Based on evidence that viral vectors increase CD8(+) T cell-mediated immunity, we also have...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
In conclusion, P. vivax plasmid DNA/Ad5 vaccine encoding blood stage parasite antigens AMA1 and MSP142 in a heterologous prime/boost immunization regimen, provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and regimen for further development. PMID: 28179404 [PubMed - as supplied by publisher]
Source: Clinical and Vaccine Immunology - Category: Allergy & Immunology Authors: Tags: Clin Vaccine Immunol Source Type: research
Abstract The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria and the CSA binding region of VAR2CSA has been identified as a promising vaccine target against placental malaria. Here we designed adenovirus encoded virus-like particles (VLP) by co-encoding Simian Immunodeficiency Virus (SIV) gag and VAR2CSA. The VAR2CSA antigen was fused to the transmembrane (TM) and cytoplasmi...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Conclusions. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types. Clinical Trials Registration. NCT01883609.
Source: The Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: PARASITES Source Type: research
Protective immunity to the liver stage of the malaria parasite can be conferred by vaccine-induced T cells, but no subunit vaccination approach based on cellular immunity has shown efficacy in field studies. We randomly allocated 121 healthy adult male volunteers in Kilifi, Kenya, to vaccination with the recombinant viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA), both encoding the malaria peptide sequence ME-TRAP (the multiple epitope string and thrombospondin-related adhesion protein), or to vaccination with rabies vaccine as a control. We gave antimalarials to clear parasitemia and con...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Reports Source Type: research
More News: Adenoviruses | Malaria | Malaria Vaccine | Parasitic Diseases | Parasitology | Study | Vaccines