An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection.

An incomplete Freund's adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response. In contrast to α-galactosyl ceramide, its synthetic analogue C34 was antagonistic toward a stimulatory effect of an aluminum hydroxide adjuvant on a specific antibody response. The aluminum hydroxide adjuvant alone could confer complete vaccine-induced protection against mortality as well as morbidity caused by a lethal challenge of the same strain of an influenza A virus. The research results indicated that adjuvants could reshape immune responses either to improve vaccine-induced immunity or to provoke an unexpected pathogenic consequence. On the basis of these observations, this research connotes the prominence to develop a precision adjuvant for innocuous vaccination aimed at generating a protective immunity without aberrant responses.

Chemical Synthesis of Truncated Capsular Oligosaccharide of Serotypes 6C and 6D of Streptococcus pneumoniae with Their Immunological Studies.

Serotypes 6C and 6D of Streptococcus pneumoniae are two major variants that cause invasive pneumococcal disease (IPD) in serogroup 6 alongside serotypes 6A and 6B. Since the introduction of the pneumococcal conjugate vaccines PCV7 and PCV13, the number of cases of IPD caused by pneumococcus in children and the elderly population has greatly decreased. However, with the widespread use of vaccines, a replacement effect has recently been observed among different serotypes and lowered the effectiveness of the vaccines. To investigate protection against the original serotypes and to explore protection against variants and replacement serotypes, we created a library of oligosaccharide fragments derived from the repeating units of the capsular polysaccharides of serotypes 6A, 6B, 6C, and 6D through chemical synthesis. The library includes nine pseudosaccharides with or without exposed terminal phosphate groups and four pseudotetrasaccharides bridged by phosphate groups. Six carbohydrate antigens related to 6C and 6D were prepared as glycoprotein vaccines for immunogenicity studies. Two 6A and two 6B glycoconjugate vaccines from previous studies were included in immunogenicity studies. We found that the conjugates containing four phosphate-bridged pseudotetrasaccharides were able to induce good immune antibodies and cross-immunogenicity by showing superior activity and broad cross-protective activity in OPKA bactericidal experiments.