Development of nanoparticle adjuvants to potentiate the immune response against diphtheria toxoid.

BACKGROUND: Over the years, diphtheria was known as contagious fatal infection caused by Corynebacterium diphtheria that affects upper respiratory system. The spread of diphtheria epidemic disease is best prevented by vaccination with diphtheria toxoid vaccine. Aluminum adjuvants were reported to stimulate the immune responses to killed and subunit vaccines. OBJECTIVE: Our study aimed to minimize adjuvant particles size, to gain insight of resulting immunity titer and impact on immune response antibody subtypes. METHODS: Aluminum salts and calcium phosphate adjuvants were prepared, followed by micro/nanoparticle adjuvants preparation. After formulation of diphtheria vaccine from diphtheria toxoid and developed adjuvants, we evaluated efficacy of these prepared vaccines based on their impact on immune response via measuring antibodies titer, antibodies isotyping and cytokines profile in immunized mice. RESULTS: A noteworthy increase in immunological parameters was observed; antibodies titer was higher in serum of mice injected with nanoparticle adjuvants-containing vaccine than mice injected with standard adjuvant-containing vaccine and commercial vaccine. Aluminum compounds adjuvants (nanoparticles and microparticles formulation) and microparticles calcium phosphate adjuvant induce TH2 response, while nanoparticles calcium phosphate and microparticles aluminum compounds adjuvants stimulate TH1 response. CONCLUSIONS: Different treatments to our adjuvant preparations (nanoparticles and microparticles formulation) had a considerable impact on vaccine immunogenicity.

Significant antibacterial activity and synergistic effects of camel lactoferrin with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-resistant Staphylococcus aureus (MRSA) causes major healthcare problems in many countries, as it is present as several hospital- and community-associated strains. Hospital-associated MRSA is one of the most prevalent nosocomial pathogens throughout the world and infections caused by community-acquired MRSA are rising. This emphasizes the need for new and efficient anti-MRSA agents. We evaluated the antibacterial effects of camel lactoferrin (cLf) and human lactoferrin (hLf) alone and in combination with several antibiotics against MRSA. Antimicrobials were tested against MRSA and an S. aureus control strain by the agar disc diffusion method. The minimum inhibitory concentration (MIC) was determined for antimicrobials by the broth microdilution method. Synergy between cLf or hLf and antibiotics was examined by checkerboard and time-kill assays. The agar disc diffusion assay showed that MRSA growth was inhibited by cLf at 0.25-3 mg/ml and hLf at 1-3 mg/ml. cLf demonstrated 3 times higher inhibitory activity against MRSA than hLf in terms of MIC values (250 vs. 750 µg/ml, respectively). Biotinylated cLf was recognized by two membrane proteins of MRSA, 66-67 KDa. Combinations of cLf or hLf and oxacillin or vancomycin at sub-MIC levels enhanced in vitro antibacterial activity against MRSA compared with each agent alone.