Immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates Plasmodium infection in mice

Ryan C. Smith, Daisy D. Colón-López, Jürgen Bosch

Research output: Contribution to journalArticle

Abstract

Background: Subtilisin-like protease 2 (SUB2) is a conserved serine protease utilized by Plasmodium parasites as a surface sheddase required for successful merozoite invasion of host red blood cells and has been implicated in ookinete invasion of the mosquito midgut. To determine if SUB2 is a suitable vaccine target to interfere with malaria parasite development, the effects of SUB2-immunization on the Plasmodium life cycle were examined in its vertebrate and invertebrate hosts.

Methods. Swiss Webster mice were immunized with SUB2 peptides conjugated to Keyhole limpet hemocyanin (KLH) or KLH alone, and then challenged with Plasmodium berghei. To determine the effects of immunization on parasite development, infected mice were evaluated by blood film and Giemsa staining. In addition, collected immune sera were used to perform passive immunization experiments in non-immunized, P. berghei-infected mice to determine the potential role of SUB2 in parasite development in the mosquito.

Results: Following P. berghei challenge, SUB2-immunized mice develop a lower parasitaemia and show improved survival when compared to control immunized mice. Moreover, SUB2 immunization results in an increase in the number of multiply invaded red blood cells, suggesting that SUB2 antibodies interfere with merozoite invasion. Passive immunization experiments imply that SUB2 may not have a major role in ookinete invasion, but this requires further investigation.

Conclusion: By interfering with red blood cell invasion, immunization against SUB2 limits malaria parasite development and confers protection from severe malaria. Together, these results provide proof-of-principle evidence for future investigation into the use of SUB2 as a vaccine or drug target to interrupt parasite development in more relevant human malaria models.

Original languageEnglish (US)
Article number313
JournalMalaria Journal
Volume13
Issue number1
DOIs
StatePublished - Aug 12 2014

Fingerprint

Merozoites
Subtilisin
Malaria
Immunization
Peptide Hydrolases
Erythrocytes
Parasites
Plasmodium berghei
Passive Immunization
Plasmodium
Culicidae
Vaccines
Parasitemia
Serine Proteases
Invertebrates
Life Cycle Stages
Vertebrates
Immune Sera

Keywords

  • Anopheles gambiae
  • Malaria
  • Plasmodium
  • Subtilisin 2

ASJC Scopus subject areas

  • Infectious Diseases
  • Parasitology

Cite this

Immunization against a merozoite sheddase promotes multiple invasion of red blood cells and attenuates Plasmodium infection in mice. / Smith, Ryan C.; Colón-López, Daisy D.; Bosch, Jürgen.

In: Malaria Journal, Vol. 13, No. 1, 313, 12.08.2014.

Research output: Contribution to journalArticle

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