A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model.
Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.
Kuklin
Nelly A
NA
Merck and Co. Inc., 440 Sumneytown Pike, WP16 100, West Point, PA 19486, USA.
Clark
Desmond J
DJ
Secore
Susan
S
Cook
James
J
Cope
Leslie D
LD
McNeely
Tessie
T
Noble
Liliane
L
Brown
Martha J
MJ
Zorman
Julie K
JK
Wang
Xin Min
XM
Pancari
Gregory
G
Fan
Hongxia
H
Isett
Kevin
K
Burgess
Bruce
B
Bryan
Janine
J
Brownlow
Michelle
M
George
Hugh
H
Meinz
Maria
M
Liddell
Mary E
ME
Kelly
Rosemarie
R
Schultz
Loren
L
Montgomery
Donna
D
Onishi
Janet
J
Losada
Maria
M
Martin
Melissa
M
Ebert
Timothy
T
Tan
Charles Y
CY
Schofield
Timothy L
TL
Nagy
Eszter
E
Meineke
Andreas
A
Joyce
Joseph G
JG
Kurtz
Myra B
MB
Caulfield
Michael J
MJ
Jansen
Kathrin U
KU
McClements
William
W
Anderson
Annaliesa S
AS
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D027682:Cation Transport Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D018805:Sepsis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D017386:Sequence Homology, Amino Acid; D013203:Staphylococcal Infections / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology* / Q000302:isolation & purification; D015996:Survival Rate
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D027682:Cation Transport Proteins; C510010:IsdB protein, Staphylococcus aureus; D013209:Staphylococcal Vaccines