Format

Send to

Choose Destination
BMC Med. 2019 Jan 30;17(1):22. doi: 10.1186/s12916-019-1255-3.

Antibody responses to merozoite antigens after natural Plasmodium falciparum infection: kinetics and longevity in absence of re-exposure.

Author information

1
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden. victor.yman@ki.se.
2
Department of Parasites and Insect Vectors, Institut Pasteur, 25-28 Rue du Dr Roux, 75015, Paris, France.
3
Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden.
4
Department of Infectious Diseases, Karolinska University Hospital, 171 76, Stockholm, Sweden.
5
Jenner Institute, University of Oxford, Oxford, OX3 7DQ, UK.
6
Kenya Medical Research Institute - Wellcome Trust Research Program, Centre for Geographic Medicine Research-Coast, PO Box 230-80108, Kilifi, Kenya.
7
Centre for Infectious Diseases, Parasitology, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany.

Abstract

BACKGROUND:

Antibodies against merozoite antigens are key components of malaria immunity. The naturally acquired antibody response to these antigens is generally considered short-lived; however, the underlying mechanisms remain unclear. Prospective studies of travellers with different levels of prior exposure, returning to malaria-free countries with Plasmodium infection, offer a unique opportunity to investigate the kinetics and composition of the antibody response after natural infection.

METHODS:

Adults diagnosed with P. falciparum malaria in Stockholm, Sweden (20 likely malaria naïve and 41 with repeated previous exposure during residency in sub-Saharan Africa) were sampled at diagnosis and 10 days and 1, 3, 6, and 12 months after treatment. Total and subclass-specific IgG responses to P. falciparum merozoite antigens (AMA-1, MSP-119, MSP-2, MSP-3, and RH5) and tetanus toxoid were measured by multiplex bead-based immunoassays and ELISA. Mathematical modelling was used to estimate the exposure-dependent longevity of antibodies and antibody-secreting cells (ASCs).

RESULTS:

A majority of individuals mounted detectable antibody responses towards P. falciparum merozoite antigens at diagnosis; however, the magnitude and breadth were greater in individuals with prior exposure. In both exposure groups, antibody levels increased rapidly for 2 weeks and decayed thereafter. Previously exposed individuals maintained two- to ninefold greater antibody levels throughout the 1-year follow-up. The half-lives of malaria-specific long-lived ASCs, responsible for maintaining circulating antibodies, ranged from 1.8 to 3.7 years for merozoite antigens and were considerably short compared to tetanus-specific ASCs. Primary infected individuals did acquire a long-lived component of the antibody response; however, the total proportion of long-lived ASCs generated in response to infection was estimated not to exceed 10%. In contrast, previously exposed individuals maintained substantially larger numbers of long-lived ASCs (10-56% of total ASCs).

CONCLUSION:

The short-lived nature of the naturally acquired antibody response, to all tested merozoite antigens, following primary malaria infection can be attributed to a combination of a poor acquisition and short half-life of long-lived ASCs. Greater longevity is acquired with repeated infections and can be explained by the maintenance of larger numbers of long-lived ASCs. These insights advance our understanding of naturally acquired malaria immunity and will guide strategies for further development of both vaccines and serological tools to monitor exposure.

KEYWORDS:

Antibody; Half-life; IgG; Longevity; Longitudinal; Malaria; Plasmodium falciparum; Serology; Subclass; Traveller

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center