Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2.
Previously we reported that calcium phosphate nanoparticles (CAP) represented a superior alternative to alum adjuvants in mice immunized with viral protein. Additionally, we showed that CAP was safe and elicited no detectable immunoglobulin E (IgE) response. In this study, we demonstrated that following mucosal delivery of herpes simplex virus type 2 (HSV-2) antigen with CAP, CAP adjuvant enhanced protective systemic and mucosal immunity versus live virus. Mice were immunized intravaginally and intranasally with HSV-2 protein plus CAP adjuvant (HSV-2+CAP), CAP alone, phosphate-buffered saline, or HSV-2 alone. HSV-2+CAP induced HSV-specific mucosal IgA and IgG and concurrently enhanced systemic IgG responses. Our results demonstrate the potency of CAP as a mucosal adjuvant. Furthermore, we show that systemic immunity could be induced via the mucosal route following inoculation with CAP-based vaccine. Moreover, neutralizing antibodies were found in the sera of mice immunized intranasally or intravaginally with HSV-2+CAP. Also, the results of our in vivo experiments indicated that mice vaccinated with HSV-2+CAP were protected against live HSV-2 infection. In conclusion, these preclinical data support the hypothesis that CAP may be an effective mucosal adjuvant that protects against viral infection.
BioSante Pharmaceuticals, Inc., Smyrna, Georgia 30082, USA. qinghe@bellsouth.net
Qing
Q
He
Alaina
A
Mitchell
Tulin
T
Morcol
Steve J D
SJ
Bell
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa; D010316:Particle Size; D014621:Vagina
D000276:Adjuvants, Immunologic; D002130:Calcium Phosphates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous