Long-Lived Antibody and B Cell Memory Responses to the Human Malaria Parasites, Plasmodium falciparum and Plasmodium vivax

Abstract

Antibodies constitute a critical component of the naturally acquired immunity that develops following frequent exposure to malaria. However, specific antibody titres have been reported to decline rapidly in the absence of reinfection, supporting the widely perceived notion that malaria infections fail to induce durable immunological memory responses. Currently, direct evidence for the presence or absence of immune memory to malaria is limited. In this study, we analysed the longevity of both antibody and B cell memory responses to malaria antigens among individuals who were living in an area of extremely low malaria transmission in northern Thailand, and who were known either to be malaria naïve or to have had a documented clinical attack of P. falciparum and/or P. vivax in the past 6 years. We found that exposure to malaria results in the generation of relatively avid antigen-specific antibodies and the establishment of populations of antigen-specific memory B cells in a significant proportion of malaria-exposed individuals. Both antibody and memory B cell responses to malaria antigens were stably maintained over time in the absence of reinfection. In a number of cases where antigen-specific antibodies were not detected in plasma, stable frequencies of antigen-specific memory B cells were nonetheless observed, suggesting that circulating memory B cells may be maintained independently of long-lived plasma cells. We conclude that infrequent malaria infections are capable of inducing long-lived antibody and memory B cell responses. It is widely perceived that immunity to malaria is short-lived, rendering people susceptible to repeated malaria infections. However, there have been very few studies on “memory” responses, how the human immune system recognizes previously encountered malaria parasites. In particular, very little is known about the durability of malaria-specific B cells and antibodies. The aim of this study was to investigate the induction and maintenance of B cell memory responses to malaria parasites in a region of Thailand where people become infected with malaria, but where the levels of malaria transmission are so low that repeated infection is uncommon. From hospital records we were able to identify people who either had been infected with malaria over the past 6 years and/or had never been infected. Blood samples were collected on four separate occasions over a period of one year and analysed by microscopy and PCR for presence of malaria parasites and by ELISA and ELISPOT for anti malarial antibodies and malaria-specific memory B cells. We found that, in a significant proportion of individuals, malaria infection results in the generation of antibodies and the establishment of populations of memory B cells against malaria parasites, which were very stably maintained over time despite the lack of any evidence of malaria reinfection. Contrary to the widely held idea that memory to malaria is suboptimally induced, our data demonstrate that B cell responses to malaria can be maintained for many years after a malaria infection and indicate that there is no inherent reason why malaria vaccines should not also induce long-lasting protection against malaria.