Infection with Plasmodium berghei boosts antibody responses primed by a DNA vaccine encoding gametocyte antigen Pbs48/45

Diana Haddad, Jorge Maciel, Nirbhay Kumar

Research output: Contribution to journalArticle

Abstract

An important consideration in the development of a malaria vaccine for individuals living in areas of endemicity is whether vaccine-elicited immune responses can be boosted by natural infection. To investigate this question, we used Plasmodium berghei ANKA blood-stage parasites for the infection of mice that were previously immunized with a DNA vaccine encoding the P. berghei sexual-stage antigen Pbs48/45. Intramuscular immunization in mice with one or two doses of DNA-Pbs48/45 or of empty DNA vaccine as control did not elicit detectable anti-Pbs48/45 antibodies as determined by enzyme-linked immunosorbent assay. An infection with P. berghei ANKA 6 weeks after DNA vaccination elicited comparable anti-Pbs48/45 antibody levels in mice which had been primed with DNA-Pbs48/45 or with empty DNA vaccine. However, a repeat infection with P. berghei ANKA resulted in significantly higher anti-Pbs48/45 antibody levels in mice which had been primed with the DNA-Pbs48/45 vaccine than the levels in the mock DNA-vaccinated mice. In parallel and as an additional control to distinguish the boosting of Pbs48/45 antibodies exclusively by gametocytes during infection, a separate group of mice primed with DNA-Pbs48/45 received an infection with P. berghei ANKA clone 2.33, which was previously described as a "nongametocyte producer." To our surprise, this parasite clone too elicited antibody levels comparable to those induced by the P. berghei gametocyte producer clone. We further demonstrate that the nongametocyte producer P. berghei clone is in fact a defective gametocyte producer that expresses Pbs48/45, much like the gametocyte producer clone, and is therefore capable of boosting antibody levels to Pbs48/45. Taken together, these results indicate that vaccine-primed antibodies can be boosted during repeat infections and warrant further investigation with additional malaria antigens.

Original languageEnglish (US)
Pages (from-to)2043-2051
Number of pages9
JournalInfection and Immunity
Volume74
Issue number4
DOIs
StatePublished - Apr 2006

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Plasmodium berghei
DNA Vaccines
Antibody Formation
Antigens
Antibodies
Clone Cells
Infection
DNA
Vaccines
Malaria Vaccines
Parasitic Diseases
Malaria
Immunization
Parasites
Vaccination
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Immunology

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Infection with Plasmodium berghei boosts antibody responses primed by a DNA vaccine encoding gametocyte antigen Pbs48/45. / Haddad, Diana; Maciel, Jorge; Kumar, Nirbhay.

In: Infection and Immunity, Vol. 74, No. 4, 04.2006, p. 2043-2051.

Research output: Contribution to journalArticle

Haddad, Diana ; Maciel, Jorge ; Kumar, Nirbhay. / Infection with Plasmodium berghei boosts antibody responses primed by a DNA vaccine encoding gametocyte antigen Pbs48/45. In: Infection and Immunity. 2006 ; Vol. 74, No. 4. pp. 2043-2051.
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