Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzaetype B vaccine comprising a synthetic antigen in healthy adults

Abstract

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and immunogenicity for a combined vaccine comprising recombinant HBV and synthetic Hib antigens. The present results support phase I-II clinical trial in the target population, two months old healthy infants.

Improving vaccines against Streptococcus pneumoniae using synthetic glycans

“…Antigen heterogeneity, batch-to-batch variation, and poorly defined conjugation to carrier proteins can be overcome when synthetic oligosaccharides are employed (11). The glycoconjugate vaccine QuimiHib, licensed in several countries to protect against Haemophilus influenzae type b, is based on a synthetic oligosaccharide resulting from chemical polymerization and is effective (12). The medicinal chemistry approach to glycoconjugate vaccine development offers an alternative to CPS isolation for a variety of glycan antigens including those for the hospital-acquired infection-causing bacteria Clostridium difficile and Klebsiella pneumoniae (13)(14)(15)(16).…”

Overexpression of O‐polysaccharide chain length regulators in Gram‐negative bacteria using the Wzx‐/Wzy‐dependent pathway enhances production of defined modal length O‐polysaccharide polymers for use as haptens in glycoconjugate vaccines

“…Chemical synthesis approaches have also been utilized to produce bacterial polysaccharide haptens of uniform size and composition (Aguilar‐Betancourt et al . ; Phalipon et al . ; Polonskaya et al .…”

Conjugation of Synthetic Trisaccharide of Staphylococcus aureus Type 8 Capsular Polysaccharide Elicits Antibodies Recognizing Intact Bacterium

“…Synthetic oligosaccharides provide an attractive alternative to furnish vaccines free of contaminants, particularly against non-culturable pathogens. Tremendous progress has been achieved in the field of developing synthetic oligosaccharide vaccines against human pathogenic bacteria (Verez- Bencomo et al, 2004;Aguilar-Betancourt et al, 2008;Shang et al, 2015;Kong et al, 2016;Liao et al, 2016;Schumann et al, 2017). Synthetic oligosaccharides with welldefined structures can facilitate epitope mapping, which allows for rational epitope design (Broecker et al, 2016).…”