Antibody and T‐cell responses associated with experimental human malaria infection or vaccination show limited relationships

Abstract

SummaryThis study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malarianaive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-1 19 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malariaspecific T-cell responses were detected in the form of interferon-c and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-c, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus antiapical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infectioninduced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related.

Validation of an IFNγ/IL2 FluoroSpot assay for clinical trial monitoring

“…ELISpot assays are very well-suited for high-throughput analyses and have become a standard technique to assess T cell responses within a clinical trial setting [ 29 , 30 ]. The applicability of the assay system in clinical practice has been confirmed with the approval of a diagnostic ELISpot for the detection of latent tuberculosis infection and disease [ 31 ].…”

Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

“…The results showed a difference in antibody production between adult and infant mice, and the levels of total antibody might contribute to rapid clearance of malarial parasites in the adult group during the chronic stage of non-lethal P.y17XNL infection. Moreover, IgG1 and IgG3 antibodies against merozoite surface proteins (MSPs) are thought to be instrumental in protection, which is considered as a major vaccine candidate [57]. Therefore, we detected the levels of P.y MSP-1 special antibody.…”

Adaptive Immune Responses Mediated Age-related Plasmodium yoelii 17XL and 17XNL Infections in 4 and 8-week-old BALB/c Mice

“…Moreover, IgG1 and IgG3 antibodies against merozoite surface proteins (MSPs) are thought to be instrumental in protection, which is considered as a major vaccine candidate [57]. Therefore, we detected the levels of P. y MSP-1 special antibody.…”