Research Articles Prime and target immunization protects against liver-stage malaria in mice

We describe an alternative "prime and target" vaccination strategy aimed specifically at inducing high numbers of tissue-resident memory T cells present in the liver at the time of hepatic infection. This approach bypasses the need for very high numbers of circulating T cells and markedly increases the efficacy of subunit immunization against liver-stage malaria with clinically relevant Ags and clinically tested viral vectors in murine challenge models. Translation to clinical use has begun, with encouraging results from a pilot safety and feasibility trial of intravenous chimpanzee adenovirus vaccination in humans. This work highlights the value of a prime-target approach for immunization against malaria and suggests that this strategy may represent a more general approach for prophylaxis or immunotherapy of other liver infections and diseases.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research

Related Links:

In this study, we investigated combining two liver-stage antigens, P. falciparum LSA1 (PfLSA1) and PfLSAP2, and investigated the induction of protective efficacy by coadministration of single-antigen vectors or vaccination with dual-antigen vectors, using simian adenovirus and modified vaccinia virus Ankara vectors. The efficacy of these vaccines was assessed in mouse malaria challenge models using chimeric P. berghei parasites expressing the relevant P. falciparum antigens and challenging mice at the peak of the T cell response. Vaccination with a combination of the single-antigen vectors expressing PfLSA1 or PfLSAP2 was ...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Microbial Immunity and Vaccines Source Type: research
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
Yenni Yusuf, Tatsuya Yoshii, Mitsuhiro Iyori, Kunitaka Yoshida, Hiroaki Mizukami, Shinya Fukumoto, Daisuke S. Yamamoto, Asrar Alam, Talha Bin Emran, Fitri Amelia, Ashekul Islam, Hiromu Otsuka, Eizo Takashima, Takafumi Tsuboi, Shigeto Yoshida
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
ConclusionsMalaria remains the most common pathogen found in febrile children in Burkina Faso. However, a relative high number of febrile children had non-malaria infections. The correct diagnosis of these non-malaria fevers is a major concern, and there is an urgent need to develop more point-of-care diagnostic tests and capacities to identify and treat the causes of these fevers.
Source: Infectious Diseases of Poverty - Category: Infectious Diseases Source Type: research
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
An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, ...
Source: Malaria Journal - Category: Infectious Diseases Authors: 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
More News: Adenoviruses | Biomedical Science | Immunotherapy | Legislation | Liver | Malaria | Malaria Vaccine | Science | Urology & Nephrology | Vaccines