IgG subclass responses to excreted-secreted antigens of Plasmodium falciparum in a low-transmission malaria area of the Peruvian Amazon

Saavedra-Langer, Rafael; Marapara, Jorge L.; Valle-Campos, Andree; Durand, Salomón; Vásquez-Chasnamote, Maria E.; Silva, Hermann; Pinedo-Cancino, Viviana

doi:10.1186/s12936-018-2471-6

Cited by 11 publications

(9 citation statements)

References 56 publications

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“…Consistent with previous studies, we showed that total IgG increased with age ( 10 ), that it substantially declined when exposure decreased, that IgG1 and IgG3 were the dominant subclasses, and that there was antigen specific bias of dominance to these subclasses ( 20 , 21 , 25 ). In addition to previous findings, we showed that the decrease in total IgG was consistently driven by the decrease in IgG3 and occasionally by a decrease in IgG1.…”

Section: Discussionsupporting

confidence: 91%

“…Antibody responses to malaria are predominantly cytophilic (IgG1 and IgG3) and have been shown to mediate effector mechanisms that inhibit of parasite growth (19,20), promote opsonic phagocytosis (21) and complement fixation (22,23). Epidemiological studies have demonstrated associations between IgG1 and IgG3 targeting various P. falciparum antigens and different manifestations of immunity, including reductions in the risk of infection, parasite density, clinical disease, and disease severity (15,20,24,25). In general, these associations were stronger for IgG3 compared to IgG1 (26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

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Impact of a Rapid Decline in Malaria Transmission on Antimalarial IgG Subclasses and Avidity

et al. 2021

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Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response. Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at two time points during high malaria transmission and two time points following a dramatic reduction in transmission. Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age. Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Impact of a Rapid Decline in Malaria Transmission on Antimalarial IgG Subclasses and Avidity

et al. 2021

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“…Consistent with previous studies, we showed that total IgG increased with age (46), that it substantially declined when exposure decreased, that IgG1 and IgG3 were the dominant subclasses, and that there was antigen specific bias of dominance to these subclasses (20,21,25). In addition to previous findings, we showed that the decrease in total IgG was consistently driven by the decrease in IgG3 and occasionally by a decrease in IgG1.…”

Section: Discussionsupporting

confidence: 91%

“…Antibody responses to malaria are predominantly cytophilic (IgG1 and IgG3) and have been shown to mediate effector mechanisms that inhibit of parasite growth (19,20), promote opsonic phagocytosis (21) ) and complement fixation (22,23). Epidemiological studies have demonstrated associations between IgG1 and IgG3 targeting various P. falciparum antigens and different manifestations of immunity, including reductions in the risk of infection, parasite density, clinical disease, and disease severity (15,20,24,25). In general, these associations were stronger for IgG3 compared to IgG1 (26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity

Ssewanyana

Rek

Rodríguez

et al. 2020

Preprint

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Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response.Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at 2 time points during high malaria transmission and 2 time points following a dramatic reduction in transmission.Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age.Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.

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“…We evaluated whether the natural antibody response to Pvs230D1M in humans would be characterized by higher levels of complement-fixing IgG subclasses. In our analyses of Pv230D1M IgG subclass frequency, IgG1 and IgG3 were shown to be the predominant subclasses during malaria infection and these isotypes are known to fix complement (29–33). This suggests that the functional activity of naturally acquired anti-Pvs230 antibody might be enhanced by complement, but this requires further investigation.…”

Section: Discussionmentioning

confidence: 73%

Naturally Acquired Antibody Response to Malaria Transmission Blocking Vaccine Candidate Pvs230 Domain 1

Tentokam¹,

Amaratunga²,

Alani³

et al. 2019

Front. Immunol.

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Plasmodium vivax malaria incidence has increased in Latin America and Asia and is responsible for nearly 74.1% of malaria cases in Latin America. Immune responses to P. vivax are less well characterized than those to P. falciparum, partly because P. vivax is more difficult to cultivate in the laboratory. While antibodies are known to play an important role in P. vivax disease control, few studies have evaluated responses to P. vivax sexual stage antigens. We collected sera or plasma samples from P. vivax-infected subjects from Brazil (n = 70) and Cambodia (n = 79) to assess antibody responses to domain 1 of the gametocyte/gamete stage protein Pvs230 (Pvs230D1M). We found that 27.1% (19/70) and 26.6% (21/79) of subjects from Brazil and Cambodia, respectively, presented with detectable antibody responses to Pvs230D1M antigen. The most frequent subclasses elicited in response to Pvs230D1M were IgG1 and IgG3. Although age did not correlate significantly with Pvs230D1M antibody levels overall, we observed significant differences between age strata. Hemoglobin concentration inversely correlated with Pvs230D1M antibody levels in Brazil, but not in Cambodia. Additionally, we analyzed the antibody response against Pfs230D1M, the P. falciparum ortholog of Pvs230D1M. We detected antibodies to Pfs230D1M in 7.2 and 16.5% of Brazilian and Cambodian P. vivax-infected subjects. Depletion of Pvs230D1M IgG did not impair the response to Pfs230D1M, suggesting pre-exposure to P. falciparum, or co-infection. We also analyzed IgG responses to sporozoite protein PvCSP (11.4 and 41.8% in Brazil and Cambodia, respectively) and to merozoite protein PvDBP-RII (67.1 and 48.1% in Brazil and Cambodia, respectively), whose titers also inversely correlated with hemoglobin concentration only in Brazil. These data establish patterns of seroreactivity to sexual stage Pvs230D1M and show similar antibody responses among P. vivax-infected subjects from regions of differing transmission intensity in Brazil and Cambodia.

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IgG subclass responses to excreted-secreted antigens of Plasmodium falciparum in a low-transmission malaria area of the Peruvian Amazon

Cited by 11 publications

References 56 publications

Impact of a Rapid Decline in Malaria Transmission on Antimalarial IgG Subclasses and Avidity

Impact of a Rapid Decline in Malaria Transmission on Antimalarial IgG Subclasses and Avidity

Impact of a rapid decline in malaria transmission on antimalarial IgG subclasses and avidity

Naturally Acquired Antibody Response to Malaria Transmission Blocking Vaccine Candidate Pvs230 Domain 1

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