Peter J. Kniskern

Comparative safety and immunogenicity of yeast recombinant hepatitis B vaccines containing S and pre-S2+S antigens

One hundred and four healthy, hepatitis B virus (HBV) seronegative males were enrolled in a single blind, randomized pilot study to compare antibody and clinical responses to a yeast recombinant pre-S2 + S vaccine and a yeast recombinant S antigen vaccine (Recombivax HBR). Participants received either a 12, 24 or 48 micrograms dose of pre-S2 + S vaccine (with a 1:5 ratio by weight of pre-S2 and S antigens) or a 10 micrograms dose of Recombivax HBR by intramuscular injection at 0, 1 and 6 months; their serological and biochemical responses were measured at 0, 1, 2, 3, 6 and 7 months, while their clinical responses were monitored for 5 days after each injection. The proportion of vaccines with minor local or systemic complaints (mainly sore arm, malaise, myalgia, fatigue) and the proportion developing antibody to surface antigen (anti-HBs) were similar for all vaccine groups. Transient elevations in alanine aminotransferase occurred infrequently. By 7 months almost all vaccinees developed anti-HBs, but titres were generally higher among recipients of pre-S2 + S vaccine. Antibody to pre-S2 antigen developed in 70-75% by 2 months and in 91-96% by 7 months. These data imply that the recombinant yeast pre-S2 + S vaccine is as well tolerated and as immunogenic as Recombivax HBR. Further studies are being conducted to assess antibody responses in larger numbers of healthy adults as well as in special populations with sub-optimal responses to currently licensed hepatitis B vaccines.

Haemophilus influenzae Type b Conjugate Vaccines

In summary, all of the Hib conjugate vaccines are highly immunogenic and efficacious in children older than 12-15 months of age, and HbOC, PRP-OMPC, and PRP-T are highly immunogenic and demonstrated to be efficacious in infants as young as 2 months old. HbOC, PRP-OMPC, and PRP-T have been licensed in numerous countries for infants and are recommended for infant immunization. However, perhaps the greatest tribute one can pay to all four Hib vaccines described in this review is to note the dramatic decrease in the incidence of Hib disease that has occurred since their introduction. In fact, according to the Morbidity and Mortality Weekly Report (March 4, 1994), the incidence of Hib disease in children less than 5 years old has declined by 95% from 41 cases per 100,000 in 1987 to 2 cases per 100,000 in 1993, timing that coincides with the availability and use of the Hib conjugate vaccines (Anderson, 1994). As universal administration is achieved and the apparent vaccine-induced reduction in carriage of Hib by the population continues, Hib vaccines may follow the lead of past vaccines (such as smallpox, measles, mumps, rubella, and polio) toward eradication of disease or at least a high degree of medical control, thereby virtually eliminating the mortality and insidious morbidity associated with invasive Hib diseases.

The Application of Molecular Biology to the Development of Novel Vaccines

In summary, we have shown that yeast is the preferred host for the expression of recombinant-derived hepatitis B vaccines, and that a yeast expression system which is productive, stable and scaleable can be developed for each of the three HBV envelope proteins. The versatility of regulated and integrated yeast expression systems in the production of foreign polypeptides with biomedical utility also has been highlighted. We also have shown that careful attention to the development of recombinant clones helps to optimize the entire production process leading to highly purified products which share many biochemical properties with the plasma-derived vaccine. Furthermore, immunization with PreS2 sequences is capable of protecting chimpanzees from HBV infection. The availability of PreS2 + S and PreS1 + PreS2 + S proteins expressed in yeast now provides the opportunity for establishing the relevance of such candidate vaccines in preventing human disease, thereby highlighting the utility of molecular biology in modern vaccine development.

Immunogenicity and safety of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis conjugate vaccine in 7.5 μg liquid formulation: a comparison of three lots with the 15.0 μg lyophilized formulation

Abstract We conducted a multicenter, single-blind, randomized comparison of the immunogenicity and safety of three manufacturing-scale lots of 7.5 μg liquid Haemophilus influenzae type b polysaccharide- Neisseria meningitidis conjugate vaccine (PRP-OMPC) and a single lot of 15.0 μg lyophilized PRP-OMPC. A total of 908 infants were entered into the study. Each infant received two primary injections intramuscularly 2 months apart beginning at age 2–6 months and a booster injection at 12–15 months. Blood samples for serology were obtained before each injection and 1 month after the second and the booster dose. Immune responses were measured by radioimmunoassay. Approximately 80% of the infants achieved a titer >1.0 μg ml −1 after the second primary dose of all four lots tested; the geometric mean titer (GMT) was ca 3 μg ml −1 for each vaccine group. After the booster dose, more than 90% of infants from each vaccine group had a titer >1.0 μg ml −1 ; GMTs ranged from 8 to 10 μg ml −1 . No serious vaccine-associated adverse reactions were reported. Thus the 7.5 μg liquid PRP-OMPC vaccine was at least as immunogenic and well tolerated as the 15.0 μg lyophilized vaccine.