scholarly journals A DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccine Encoding Thrombospondin-Related Adhesion Protein but Not Circumsporozoite Protein Partially Protects Healthy Malaria-Naive Adults against Plasmodium falciparum Sporozoite Challenge

2006 ◽  
Vol 74 (10) ◽  
pp. 5933-5942 ◽  
Author(s):  
S. J. Dunachie ◽  
M. Walther ◽  
J. E. Epstein ◽  
S. Keating ◽  
T. Berthoud ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccinia Virus ◽  
Ex Vivo ◽  
Circumsporozoite Protein ◽  
Elispot Response ◽  
Adhesion Protein ◽  
Modified Vaccinia Virus Ankara ◽  
Boost Vaccine ◽  
Falciparum Sporozoite ◽  
Ifn Γ

ABSTRACT The safety, immunogenicity, and efficacy of DNA and modified vaccinia virus Ankara (MVA) prime-boost regimes were assessed by using either thrombospondin-related adhesion protein (TRAP) with a multiple-epitope string ME (ME-TRAP) or the circumsporozoite protein (CS) of Plasmodium falciparum. Sixteen healthy subjects who never had malaria (malaria-naive subjects) received two priming vaccinations with DNA, followed by one boosting immunization with MVA, with either ME-TRAP or CS as the antigen. Immunogenicity was assessed by ex vivo gamma interferon (IFN-γ) enzyme-linked immunospot assay (ELISPOT) and antibody assay. Two weeks after the final vaccination, the subjects underwent P. falciparum sporozoite challenge, with six unvaccinated controls. The vaccines were well tolerated and immunogenic, with the DDM-ME TRAP regimen producing stronger ex vivo IFN-γ ELISPOT responses than DDM-CS. One of eight subjects receiving the DDM-ME TRAP regimen was completely protected against malaria challenge, with this group as a whole showing significant delay to parasitemia compared to controls (P = 0.045). The peak ex vivo IFN-γ ELISPOT response in this group correlated strongly with the number of days to parasitemia (P = 0.033). No protection was observed in the DDM-CS group. Prime-boost vaccination with DNA and MVA encoding ME-TRAP but not CS resulted in partial protection against P. falciparum sporozoite challenge in the present study.

scholarly journals Safety, Immunogenicity, and Efficacy of Prime-Boost Immunization with Recombinant Poxvirus FP9 and Modified Vaccinia Virus Ankara Encoding the Full-Length Plasmodium falciparum Circumsporozoite Protein

2006 ◽  
Vol 74 (5) ◽  
pp. 2706-2716 ◽  
Author(s):  
Michael Walther ◽  
Fiona M. Thompson ◽  
Susanna Dunachie ◽  
Sheila Keating ◽  
Stephen Todryk ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Circumsporozoite Protein ◽  
Fowlpox Virus ◽  
Partial Protection ◽  
Modified Vaccinia Virus Ankara ◽  
Boost Immunization ◽  
Recombinant Fowlpox Virus ◽  
First Time

ABSTRACT Heterologous prime-boost immunization with DNA and various recombinant poxviruses encoding malaria antigens is capable of inducing strong cell-mediated immune responses and partial protection in human sporozoite challenges. Here we report a series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes. For the first time, these vaccines were administered intramuscularly and at doses of up to 5 × 108 PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.

scholarly journals Novel Recombinant Mycobacterium bovis BCG, Ovine Atadenovirus, and Modified Vaccinia Virus Ankara Vaccines Combine To Induce Robust Human Immunodeficiency Virus-Specific CD4 and CD8 T-Cell Responses in Rhesus Macaques

2010 ◽  
Vol 84 (12) ◽  
pp. 5898-5908 ◽  
Author(s):  
Maximillian Rosario ◽  
Richard Hopkins ◽  
John Fulkerson ◽  
Nicola Borthwick ◽  
Máire F. Quigley ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Mycobacterium Bovis ◽  
Ex Vivo ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1

ABSTRACT Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.

scholarly journals Naturally Exposed Populations Differ in Their T1 and T2 Responses to the Circumsporozoite Protein of Plasmodium falciparum

2002 ◽  
Vol 70 (3) ◽  
pp. 1468-1474 ◽  
Author(s):  
W. H. H. Reece ◽  
M. Plebanski ◽  
P. Akinwunmi ◽  
P. Gothard ◽  
K. L. Flanagan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Affect Regulation ◽  
Elispot Assay ◽  
T Cell Responses ◽  
Circumsporozoite Protein ◽  
Interleukin 4 ◽  
Cell Responses ◽  
Ifn Γ ◽  
T1 And T2

ABSTRACT T-cell responses directed against the circumsporozoite protein (CS) of Plasmodium falciparum can mediate protection against malaria. We determined the frequency of T cells reactive to different regions of the CS in the blood of donors naturally exposed to P. falciparum by examining T1 (gamma interferon [IFN-γ] ELISPOT assay), T2 (interleukin 4 [IL-4] ELISPOT assay), and proliferative T-cell responses. The proliferative responses were weak, which confirmed previous observations. The responses to the CS in the IL-4 and IFN-γ ELISPOT assays were also weak (<40 responding cells per 106 cells), much weaker than the response to the purified protein derivative of Mycobacterium tuberculosis in the same donors. Moreover, a response in one assay could not be used to predict a response in either of the other assays, suggesting that although these assays may measure different responding cells, all of the responses are weakly induced by natural exposure. Interestingly, the two different study populations used had significantly different T1 and T2 biases in their responses in the C terminus of the protein, suggesting that the extent of P. falciparum exposure can affect regulation of the immune system.

scholarly journals Heterologous Priming-Boosting with DNA and Modified Vaccinia Virus Ankara Expressing Tryparedoxin Peroxidase Promotes Long-Term Memory against Leishmania major in Susceptible BALB/c Mice

2006 ◽  
Vol 75 (2) ◽  
pp. 852-860 ◽  
Author(s):  
Carmel B. Stober ◽  
Uta G. Lange ◽  
Mark T. M. Roberts ◽  
Antonio Alcami ◽  
Jenefer M. Blackwell
Keyword(s):  
Vaccinia Virus ◽  
Leishmania Major ◽  
Long Term Memory ◽  
Effector Phase ◽  
Modified Vaccinia Virus Ankara ◽  
Tryparedoxin Peroxidase ◽  
Memory Phase ◽  
Ifn Γ ◽  
Susceptible Populations

ABSTRACT Leishmaniasis affects 12 million people, but there are no vaccines in routine clinical use. Th1 polarizing vaccines that elicit long-term protection are required to prevent disease in susceptible populations. We recently showed that heterologous priming-boosting with tryparedoxin peroxidase (TRYP) DNA followed by TRYP-modified vaccinia virus Ankara (TRYP MVA) protected susceptible BALB/c mice from Leishmania major. Here we compared treatment with TRYP DNA with treatment with TRYP DNA/TRYP MVA. We found that equivalent levels of protection during the postvaccination effector phase correlated with equivalent levels of serum immunoglobulin G2a and gamma interferon (IFN-γ) in draining lymph nodes. In contrast, challenge infection during the memory phase revealed that there was enhanced clinical efficacy with TRYP DNA/TRYP MVA. This correlated with higher levels of effector phase splenic IFN-γ, sustained prechallenge levels of memory phase IFN-γ, and a more polarized post-L. major challenge Th1 response compared to the Th2/Treg response. Thus, TRYP DNA/TRYP MVA, but not TRYP DNA alone, provides long-term protection against murine leishmaniasis.

scholarly journals Measuring naturally acquired ex vivo IFN-γ responses to Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (CelTOS) in Ghanaian adults

2015 ◽  
Vol 14 (1) ◽  
pp. 20 ◽  
Author(s):  
Dorothy Anum ◽  
Kwadwo A Kusi ◽  
Harini Ganeshan ◽  
Michael R Hollingdale ◽  
Michael F Ofori ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Ex Vivo ◽  
Ifn Γ
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