Recognition of pneumococcal isolates by antisera raised against PspA fragments from different clades.
Pneumococcal surface protein A (PspA) is an important vaccine candidate against pneumococcal infections, capable of inducing protection in different animal models. Based on its structural diversity, it has been suggested that a PspA-based vaccine should contain at least one fragment from each of the two major families (family 1, comprising clades 1 and 2, and family 2, comprising clades 3, 4 and 5) in order to elicit broad protection. This study analysed the recognition of a panel of 35 pneumococcal isolates bearing different PspAs by antisera raised against the N-terminal regions of PspA clades 1 to 5. The antiserum to PspA clade 4 was found to show the broadest cross-reactivity, being able to recognize pneumococcal strains containing PspAs of all clades in both families. The cross-reactivity of antibodies elicited against a PspA hybrid including the N-terminal region of clade 1 fused to a shorter and more divergent fragment (clade-defining region, or CDR) of clade 4 (PspA1-4) was also tested, and revealed a strong recognition of isolates containing clades 1, 4 and 5, and weaker reactions with clades 2 and 3. The analysis of serum reactivity against different PspA regions further revealed that the complete N-terminal region rather than just the CDR should be included in an anti-pneumococcal vaccine. A PspA-based vaccine is thus proposed to be composed of the whole N-terminal region of clades 1 and 4, which could also be expressed as a hybrid protein.
Darrieux
Michelle
M
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05509-900, São Paulo, SP, Brazil.
Moreno
Adriana T
AT
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05509-900, São Paulo, SP, Brazil.
Ferreira
Daniela M
DM
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05509-900, São Paulo, SP, Brazil.
Pimenta
Fabiana C
FC
Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Brazil.
de Andrade
Ana Lúcia S S
ALSS
Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Brazil.
Lopes
Alexandre P Y
APY
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05509-900, São Paulo, SP, Brazil.
Leite
Luciana C C
LCC
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05509-900, São Paulo, SP, Brazil.
Miyaji
Eliane N
EN
Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05509-900, São Paulo, SP, Brazil.
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000276:immunology* / Q000302:isolation & purification
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D011994:Recombinant Proteins; C051592:pneumococcal surface protein A