Neisseria meningitidis is a life-threatening pathogen that causes meningitis and other clinical manifestations. Drug resistance resulting from antibiotic abuse in recent years has caused the shift from drug cures of diseases to vaccination prevention, regarding to the pathogen. As a key virulence determinant, meningococcal capsular polysaccharide (PS) has been used to prevent these diseases for many years. Conjugation of PS to a carrier protein has been used to improve the immunogenicity of PS and to induce memory response in infants and young children.

The conventional conjugation scheme, using adipic acid dihydrazide (ADH) as the spacer arm, suffers from serious side reactions and low conjugation efficiency. In the meantime, the short spacer arm leads to serious steric shielding of antigenic PS epitopes by carrier protein, and due to the low PS immunogenicity and conjugate vaccines must be multi-vaccinated (3 or 4 needles).

To address these questions, Dr. Huang Q. from Prof. Hu Tao’s group of Institute of Process Engineering (IPE), Chinese Academy of Sciences used a heterobifunctional polyethylene glycol (PEG) as a spacer arm to conjugate meningococcal group Y capsular PS with tetanus toxoid (TT). On one hand, the PEG spacer arm greatly increased PS immunogenicity by fully decreasing the steric shielding effect of TT on antigenic epitopes of PS. On the other hand, PEG prolonged the immune persistence of the conjugate vaccine by prolonging its circulating half-life and as a result, afforded some possibility of reduced vaccinations of the vaccine. In addition, the heterobifunctional reagent reduced side reactions and consequently increased conjugate yield. The research provided an important basis for developing more effective PS conjugate vaccine benefiting from PEG to prevent bacterial infection.

The study entitled “PEG as a spacer arm markedly increases the immunogenicity of meningococcal group Y polysaccharide conjugate vaccine” was published on Journal of Controlled Release(2013, 172: 382-389)

(Image By IPE)