Factors influencing the induction of high affinity antibodies to Plasmodium falciparum merozoite antigens and how affinity changes over time

Tijani, Muyideen K.; Reddy, Sreenivasulu B.; Langer, Christine; Beeson, James G.; Wahlgren, Mats; Nwuba, Roseangela I.; Persson, Kristina

doi:10.1038/s41598-018-27361-w

Cited by 19 publications

(14 citation statements)

References 54 publications

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“…The production of high affinity antibodies is an indication of successful priming by an antigen and indicates that B-cell clones specific to such antigens have undergone affinity maturation. A recent study found variation in affinity to different antigens over time and differential antibody affinity to different antigens [85]. Since Env and Gag induces differential immune responses, their antibody affinity maturation process should also be different.…”

Section: Discussionmentioning

confidence: 99%

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

et al. 2020

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Studies have shown that blockade of CTLA-4 promoted the expansion of germinal center B-cells in viral infection or immunization with model antigens. Few studies have evaluated the immunological consequences of CTLA-4 blockade during immunization against relevant vaccine candidates. Here, we investigated the effects of CTLA-4 blockade on HIV virus-like particles (VLPs) vaccination in a C57BL/6J mouse model. We found that CTLA-4 blockade during HIV VLP immunization resulted in increased CD4+ T-cell activation, promoted the expansion of HIV envelope (Env)-specific follicular helper T cell (Tfh) cells, and significantly increased HIV Gag- and Env-specific IgG with higher avidity and antibody-dependent cellular cytotoxicity (ADCC) capabilities. Furthermore, after only a single immunization, CTLA-4 blockade accelerated T-cell dependent IgG class switching and the induction of significantly high serum levels of the B-cell survival factor, A proliferation-inducing ligand (APRIL). Although no significant increase in neutralizing antibodies was observed, increased levels of class-switched Env- and Gag-specific IgG are indicative of increased polyclonal B-cell activation, which demonstrated the ability to mediate and enhance ADCC in this study. Altogether, our findings show that CTLA-4 blockade can increase the levels of HIV antigen-specific B-cell and antigen-specific Tfh cell activity and impact humoral immune responses when combined with a clinically relevant HIV VLP-based vaccine.

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Section: Discussionmentioning

confidence: 99%

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

et al. 2020

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“…Interestingly, the amount of NH 4 SCN needed to release 50% of bound Ab was quite similar for Ab-positive infants and adults (Table 1), although lower amounts of chaotrope were required for infants for AMA1 and EBA-175, slightly lower for MSP1-42, but similar for MSP2 and MSP3 (Table 1). Studies in high transmission areas have reported little or no increase in Ab avidity with age for EBA-175, MSP1, MSP2, and MSP3 [4][5][6][7][8][9]. Plasma used in this study was from infants and adults living in a rural village with perennial transmission who received an estimated 257 infectious mosquito bites/person/year [29,30].…”

Section: Discussionmentioning

confidence: 99%

“…Early studies showed that Ab avidity to an extract of P. falciparum-infected erythrocytes increased after a few infections in a low transmission region [2,3]. However, in high transmission areas, most studies have found little or no increase in antibody avidity with age to merozoite antigens, including MSP1, MSP2, MSP3 and EBA-175 [4][5][6][7][8][9], although an increase with age for AMA1 has been reported [4,5]. Thus, there is much to be learned about the role of Ab avidity in immunity to malaria.…”

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confidence: 99%

“…A variety of protocols have been used to study antibody avidity. Although a few investigators have employed plasma magnetic resonance or bilayer interferometry [4,7,10], most studies have used the ELISA format with different concentrations of chaotropic agents [2,3,5,6,8,9,[11][12][13][14][15][16][17]. In these assays, results are often expressed as an Avidity Index (AI), defined as the amount (e.g., O.D.)…”

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confidence: 99%

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Measuring antibody avidity to Plasmodium falciparum merozoite antigens using a multiplex immunoassay approach

Taylor

Bobbili

Kayatani

et al. 2020

Malar J

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Background: Antibodies (Ab) play a significant role in immunity to Plasmodium falciparum malaria. Usually, following repeated exposure to pathogens, affinity maturation and clonal selection take place, resulting in increased antibody avidity. However, some studies suggest affinity maturation may not occur to malaria antigens in endemic areas. Information on development of antibody avidity is confusing and conflicting, in part, because different techniques have been used to measure avidity. Today, bead-based multiplex immunoassays (MIA) are routinely used to simultaneously quantitate antibody levels to multiple antigens. This study evaluated the feasibility of developing an avidity MIA with 5 merozoite antigens (AMA1, EBA-175, MSP1-42, MSP2, MSP3) that uses a single chaotropic concentration. Methods: The most common ELISA protocols that used the chaotropic reagents guanidine HCl (GdHCl), urea, and ammonium thiocyanate (NH 4 SCN) were adapted to a multiplex MIA format. Then, different concentrations of chaotropes and incubation times were compared and results were expressed as an Avidity Index (AI), i.e., percentage of antibody remaining bound in the presence of chaotrope. Experiments were conducted to (i) identify the assay with the widest range of AI (discriminatory power), (ii) determine the amount of chaotrope needed to release 50% of bound Ab using plasma from adults and infants, and (iii) evaluate assay repeatability. Results: Overall, 4 M GdHCl and 8 M urea were weaker chaotropes than 3 M NH 4 SCN. For example, they failed to release significant amounts of Ab bound to MSP1-42 in adult plasma samples; whereas, a range of AI values was obtained with NH 4 SCN. Titration of NH 4 SCN revealed that 2 M NH 4 SCN gave the widest range of AI for the 5 antigens. Binding studies using plasma from 40 adults and 57 1-year old infants in Cameroon showed that 2.1 M ± 0.32 (mean ± SD) NH 4 SCN (adults) and 1.8 M ± 0.23 M (infants) released 50% of bound Ab from the merozoite antigens. Conclusions: An avidity MIA is feasible for the 5 merozoite antigens that uses a single concentration (2 M) of NH 4 SCN. The assay provides a simple method to quickly obtain information about Ab quantity and quality in the acquisition of immunity to malaria in endemic populations.

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“…In Nigeria, affinity of antibody binding to PfRH2, measured using surface plasmon resonance, correlated with antibody inhibition of merozoite invasion, and IgG from exposed adults inhibited growth of PfRH2 transgenic parasites in allele‐specific or allele‐independent patterns, depending on the IgG source …”

Section: Functional Antibody In Malariamentioning

confidence: 99%

Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks

2020

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Many parasitic infections stimulate antibody responses in their mammalian hosts. The ability of these antibodies to protect against disease varies markedly. Research has revealed that functional properties of antibodies determine their role in protection against parasites. Investigations of antibodies against Plasmodium spp. have demonstrated a variety of functional activities, ranging from invasion inhibition and parasite growth inhibition to antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. These activities have been demonstrated with a large variety of parasite molecules at multiple life cycle stages, highlighting the importance of functional antibody responses in malaria. Other parasitic infections have not yet been investigated in similar detail, but these mechanisms are likely to operate in nonmalarial parasitic infections as well. In this report, we review data on the role of functional antibody responses in protection from parasitic infections, highlighting discoveries in malaria, a parasite for which our knowledge base is the most advanced.

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Factors influencing the induction of high affinity antibodies to Plasmodium falciparum merozoite antigens and how affinity changes over time

Cited by 19 publications

References 54 publications

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

Measuring antibody avidity to Plasmodium falciparum merozoite antigens using a multiplex immunoassay approach

Antibody effector functions in malaria and other parasitic diseases: a few needles and many haystacks

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