John J. Donnelly

Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants.

OBJECTIVEnTo evaluate the safety, immunogenicity, and immunologic memory in young infants of a seven-valent (6B, 14, 19F, 23F, 18C, 4, 9V) pneumococcal vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis. VACCINEES: Healthy 2-month-old infants 12- to 15-month-old control infants were recruited from participating private practices.nnnMETHODSnInfants (n = 25) were vaccinated at 2, 4, and 6 months of age with the conjugated pneumococcal vaccine, followed by a single dose of licensed pneumococcal polysaccharide vaccine (n = 20) at 12 to 15 months of age. Thirteen infants who had not received the investigational pneumococcal conjugate vaccine served as control subjects and were given a single dose of the licensed pneumococcal polysaccharide vaccine at 12 to 15 months of age.nnnRESULTSnThe investigational pneumococcal conjugate vaccine was well tolerated by infants. The vaccine was highly immunogenic in young infants, with significant increases in antibody to all seven serotypes after either two or three injections. At 12 to 15 months of age, infants who had been primed with the investigational pneumococcal conjugate vaccine had a brisk immunologic response to the booster injection of the licensed pneumococcal polysaccharide vaccine. Control infants, who received a single primary injection of the licensed pneumococcal polysaccharide vaccine, had negligible immunologic responses to four of the seven serotypes and low responses to the other three types.nnnCONCLUSIONnThe investigational seven-valent pneumococcal conjugate vaccine administered to young infants was well tolerated and highly immunogenic and provided immunologic memory to an injection of the licensed pneumococcal polysaccharide vaccine.

DNA Vaccines for Bacteria and Viruses

DNA vaccines are nonreplicating plasmids encoding genes from pathogens. The antigenic proteins are thus expressed in the cells of the vaccinated host and result in the generation of both antibody and cell-mediated immune responses. The ability to generate proteins with native conformation contrasts with certain recombinant protein or inactivated viral vaccines, and offers the means to generate antibodies against the relevant epitopes. Because the desired proteins are synthesized within the host, cell-mediated immune responses can be generated, without the inherent risks of certain viral vectors or of attenuation of certain attenuated viruses (e.g., HIV) and bacteria.

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.

Vaccination with Polynucleotides: A Novel Means of Generating Immunity

Several areas of vaccine research and development have shown promising results recently, including new and improved adjuvants to induce or enhance immune responses against inoculated antigens, formulations to achieve slow release of antigens, and delivery systems to target antigens for the generation of specific types of immune responses, such as cell-mediated or mucosal responses. The genesis of cell-mediated immune responses requires presentation of antigens by major histocompatibility complex (MHC) class I molecules, which is generally accomplished by processing of endogenously expressed antigens (e.g. during a virus infection). Therefore, vaccines designed to elicit such immune responses need to consist of recombinant expression vectors or a means of delivering exogenous proteins into the intracellular MHC class I processing pathway. Extracellular antigens can be targeted for presentation by MHC class I using immunostimulating complexes (Takahashi et al., 1990), saponin adjuvants (Newman et al., 1992), synthetic lipopeptides (Deres et al., 1992), pH sensitive liposomes (Collins et al., 1992), and recombinant fusion proteins (Donnelly et al., 1993), which in some cases has been shown to lead to the generation of cytotoxic T lymphocyte (CTL) responses after administration in vivo. Synthesis of foreign antigens in vivo has been attained using attenuated live viruses or live organisms that have been genetically manipulated to express inserted genes.