Acquired immune responses to three malaria vaccine candidates and their relationship to invasion inhibition in two populations naturally exposed to malaria

AbstractGenetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.

Download Full-text

Plasmodium falciparum Malaria in Children Aged 0-2 Years: The Role of Foetal Haemoglobin and Maternal Antibodies to Two Asexual Malaria Vaccine Candidates (MSP3 and GLURP)

PLoS ONE ◽

10.1371/journal.pone.0107965 ◽

2014 ◽

Vol 9 (9) ◽

pp. e107965 ◽

Cited By ~ 19

Author(s):

David Tiga Kangoye ◽

Issa Nebie ◽

Jean-Baptiste Yaro ◽

Siaka Debe ◽

Safiatou Traore ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Malaria Vaccine ◽

Plasmodium Falciparum Malaria ◽

Maternal Antibodies ◽

Foetal Haemoglobin ◽

Vaccine Candidates

Download Full-text

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Clinical and Vaccine Immunology ◽

10.1128/cvi.00565-15 ◽

2015 ◽

Vol 23 (2) ◽

pp. 84-94 ◽

Cited By ~ 22

Author(s):

David R. Martinez ◽

Sallie R. Permar ◽

Genevieve G. Fouda

Keyword(s):

Immune Responses ◽

Hiv Infection ◽

Vaccine Efficacy ◽

Neutralizing Antibody ◽

Hiv Vaccine ◽

Antibody Responses ◽

Hiv Vaccines ◽

Vaccine Candidates ◽

Protective Antibodies ◽

Pediatric Populations

ABSTRACTExtensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

Download Full-text

Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells

Blood ◽

10.1182/blood-2010-01-264150 ◽

2010 ◽

Vol 116 (26) ◽

pp. 5875-5884 ◽

Cited By ~ 30

Author(s):

Hideaki Tanizaki ◽

Gyohei Egawa ◽

Kayo Inaba ◽

Tetsuya Honda ◽

Saeko Nakajima ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

T Cell ◽

Immune Responses ◽

Lymph Nodes ◽

Actin Polymerization ◽

Cell Stimulation ◽

T Cell Stimulation ◽

Acquired Immune Responses

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

Download Full-text

Expansion of Functional Myeloid-Derived Suppressor Cells in Controlled Human Malaria Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.625712 ◽

2021 ◽

Vol 12 ◽

Author(s):

Carlos Lamsfus Calle ◽

Rolf Fendel ◽

Anurag Singh ◽

Thomas L. Richie ◽

Stephen L. Hoffman ◽

...

Keyword(s):

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Immune Responses ◽

Malaria Infection ◽

Malaria Vaccine ◽

Suppressor Cells ◽

T Cell Proliferation ◽

Myeloid Derived Suppressor Cells ◽

Controlled Human Malaria Infection

Malaria can cause life-threatening complications which are often associated with inflammatory reactions. More subtle, but also contributing to the burden of disease are chronic, often subclinical infections, which result in conditions like anemia and immunologic hyporesponsiveness. Although very frequent, such infections are difficult to study in endemic regions because of interaction with concurrent infections and immune responses. In particular, knowledge about mechanisms of malaria-induced immunosuppression is scarce. We measured circulating immune cells by cytometry in healthy, malaria-naïve, adult volunteers undergoing controlled human malaria infection (CHMI) with a focus on potentially immunosuppressive cells. Infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) were inoculated during two independent studies to assess malaria vaccine efficacy. Volunteers were followed daily until parasites were detected in the circulation by RT-qPCR. This allowed us to analyze immune responses during pre-patency and at very low parasite densities in malaria-naïve healthy adults. We observed a consistent increase in circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in volunteers who developed P. falciparum blood stage parasitemia. The increase was independent of preceding vaccination with a pre-erythrocytic malaria vaccine. PMN-MDSC were functional, they suppressed CD4+ and CD8+ T cell proliferation as shown by ex-vivo co-cultivation with stimulated T cells. PMN-MDSC reduced T cell proliferation upon stimulation by about 50%. Interestingly, high circulating PMN-MDSC numbers were associated with lymphocytopenia. The number of circulating regulatory T cells (Treg) and monocytic MDSC (M-MDSC) showed no significant parasitemia-dependent variation. These results highlight PMN-MDSC in the peripheral circulation as an early indicator of infection during malaria. They suppress CD4+ and CD8+ T cell proliferation in vitro. Their contribution to immunosuppression in vivo in subclinical and uncomplicated malaria will be the subject of further research. Pre-emptive antimalarial pre-treatment of vaccinees to reverse malaria-associated PMN-MDSC immunosuppression could improve vaccine response in exposed individuals.

Download Full-text

Essential functions of Runx/Cbfβ in gut conventional dendritic cells for priming Rorγt+ T cells

Life Science Alliance ◽

10.26508/lsa.201900441 ◽

2019 ◽

Vol 3 (1) ◽

pp. e201900441 ◽

Cited By ~ 2

Author(s):

Mari Tenno ◽

Alicia Yoke Wei Wong ◽

Mika Ikegaya ◽

Eiji Miyauchi ◽

Wooseok Seo ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Immune Responses ◽

Cell Polarization ◽

Th Cells ◽

Th Cell ◽

Intrinsic Mechanism ◽

Specific Effector ◽

Acquired Immune Responses ◽

Type 3

Acquired immune responses are initiated by activation of CD4+ helper T (Th) cells via recognition of antigens presented by conventional dendritic cells (cDCs). DCs instruct Th-cell polarization program into specific effector Th subset, which will dictate the type of immune responses. Hence, it is important to unravel how differentiation and/or activation of DC are linked with Th-cell–intrinsic mechanism that directs differentiation toward a specific effector Th subset. Here, we show that loss of Runx/Cbfβ transcription factors complexes during DC development leads to loss of CD103+CD11b+ cDC2s and alters characteristics of CD103−CD11b+ cDCs in the intestine, which was accompanied with impaired differentiation of Rorγt+ Th17 cells and type 3 Rorγt+ regulatory T cells. We also show that a Runx-binding enhancer in the Rorc gene is essential for T cells to integrate cDC-derived signals to induce Rorγt expression. These findings reveal that Runx/Cbfβ complexes play crucial and complementary roles in cDCs and Th cells to shape converging type 3 immune responses.

Download Full-text

A Universal Bacteriophage T4 Nanoparticle Platform to Design Multiplex SARS-CoV-2 Vaccine Candidates by CRISPR Engineering

10.1101/2021.01.19.427310 ◽

2021 ◽

Author(s):

Jingen Zhu ◽

Neeti Ananthaswamy ◽

Swati Jain ◽

Himanshu Batra ◽

Wei-Chun Tang ◽

...

Keyword(s):

Immune Responses ◽

Bacteriophage T4 ◽

Universal Vaccine ◽

Nucleocapsid Proteins ◽

Vaccine Candidates ◽

Receptor Interactions ◽

New Type ◽

Nanoparticle Structure ◽

Viral Components ◽

Rapid Deployment

AbstractA “universal” vaccine design platform that can rapidly generate multiplex vaccine candidates is critically needed to control future pandemics. Here, using SARS-CoV-2 pandemic virus as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates were engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include: expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers is found to be the most potent vaccine candidate in mouse and rabbit models. Without any adjuvant, this vaccine stimulated robust immune responses, both TH1 and TH2 IgG subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new type of nanovaccine design framework might allow rapid deployment of effective phage-based vaccines against any emerging pathogen in the future.

Download Full-text