5 research outputs found
Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine in human immune system mice
No full textAbstractA number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic Plasmodium berghei sporozoites expressing full-length PfCSP and found that AdPfCSP-immunized (but not naïve) mice were protected against subsequent malaria challenge. The level of the HLA-A∗0201-restricted, PfCSP-specific human CD8+ T-cell response was closely correlated with the level of malaria protection. Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice almost completely abolished the anti-malaria immune response. Taken together, our data show that human CD8+ T cells mediate protective anti-malaria immunity in vivo
Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes
No full textAmajorityofPlasmodiumfalciparumstrainsinvadeerythrocytesthroughinteractionswithsialicacid(SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasionreceptorofmanylaboratorystrainsofP.falciparum.TodeterminetheroleofCR1inerythrocyte invasion among P. falciparum field isolates, we tested eight isolates obtained from children in Kenya. All the parasites examined were capable of invading in a SA-independent manner, and invasion of neuraminidase-treatederythrocyteswasnearlycompletelyblockedbyanti-CR1andsolubleCR1(sCR1). Inaddition,anti-CR1andsCR1partiallyinhibitedinvasionofintacterythrocytesinamajorityofisolates tested. Sequencing of the hypervariable region of P. falciparum AMA-1 showed considerable diversity among all the isolates. These data demonstrate that CR1 mediates SA-independent erythrocyte invasion in P. falciparum field isolates.AmajorityofPlasmodiumfalciparumstrainsinvadeerythrocytesthroughinteractionswithsialicacid(SA) on glycophorins. However, we recently reported that complement receptor 1 (CR1) is a SA-independent invasionreceptorofmanylaboratorystrainsofP.falciparum.TodeterminetheroleofCR1inerythrocyte invasion among P. falciparum field isolates, we tested eight isolates obtained from children in Kenya. All the parasites examined were capable of invading in a SA-independent manner, and invasion of neuraminidase-treatederythrocyteswasnearlycompletelyblockedbyanti-CR1andsolubleCR1(sCR1). Inaddition,anti-CR1andsCR1partiallyinhibitedinvasionofintacterythrocytesinamajorityofisolates tested. Sequencing of the hypervariable region of P. falciparum AMA-1 showed considerable diversity among all the isolates. These data demonstrate that CR1 mediates SA-independent erythrocyte invasion in P. falciparum field isolates
Author Correction: Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity
No full textIn the original version of the article, Fig. 2b was mislabelled. The second row was incorrectly labelled as “MiMPL > MiPBS and MiQS ≈ MPBS” this has now been corrected to “MiQS-21 > MiPBS and MiMPL ≈ MiPBS”. The third row was incorrectly labelled as “MiQS21 > MiPBS and MiMPL ≈ MiPBS” this has now been corrected to “MiMPL > MiPBS and MiQS-21 ≈ MiPBS”. These errors have now been corrected in the PDF and HTML versions of this article.</jats:p
Author Correction: Antibody responses to the RTS,S/AS01(E) vaccine and Plasmodium falciparum antigens after a booster dose within the phase 3 trial in Mozambique
No full textLimited antigenic diversity of Plasmodium falciparumapical membrane antigen 1 supports the development of effective multi-allele vaccines
No full textBackground: Polymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies. Methods: We aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence. Results: We found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis. Conclusions: Antigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines
