Secondary Response to Booster Injection of Alum-Precipitated Tetanus Toxoid

ABSTRACT Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r = 0.741,r = 0.653, respectively; n = 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.

Download Full-text

The role of lymphocytes in antibody formation V. Transfer of immunological memory to tetanus toxoid: the origin of plasma cells from small lymphocytes, stimulation of memory cells in vitro and the persistence of memory after cell-transfer

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1973.0009 ◽

1973 ◽

Vol 183 (1071) ◽

pp. 125-139 ◽

Cited By ~ 6

Keyword(s):

Tetanus Toxoid ◽

Thoracic Duct ◽

Plasma Cells ◽

Serum Antibody ◽

Immunological Memory ◽

Secondary Response ◽

Memory Cells ◽

Splenic Red Pulp

Immunological memory to tetanus toxoid was transferred to heavily irradiated rats by thoracic duct lymphocytes (TDL) from primarily immunized donors. The recipients generated substantial serum antibody responses when they were challenged with antigen and at the height of the response accumulations of specifically fluorescent plasma cells had developed in the splenic red pulp. When F 1 hybrid TDL were transferred to irradiated parental-strain animals it was possible to determine the origin of the specifically fluorescent cells in the spleen by observing the damage inflicted on them in vitro by alloantisera and complement. The analysis showed that all the antibody-forming cells were of donor origin; in morphological terms the experiments established that small lymphocytes develop by differentiation and division into plasma cells. Secondary responses to tetanus toxoid were also observed when TDL were incubated with antigen in vitro , washed thoroughly and then transferred to irradiated animals without further antigenic challenge. These experiments suggested that macrophages were not essential for the induction of the secondary response. Irradiated rats given TDL from immunized donors 4 weeks previously yielded, in turn, TDL capable of transferring immunological memory to further irradiated animals. This implicates long-lived lymphocytes as the carriers of memory. Further, it was shown that the secondary responsiveness conferred on irradiated animals by TDL was not diminished by chronic drainage of cells from a thoracic duct fistula, a procedure which severely depletes recirculating lymphocytes. This phenomenon has also been observed in actively immunized animals. These observations raise the possibility that recirculating memory cells may with draw into lymphoid tissue and become sessile for part of their life history.

Download Full-text

GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO

Journal of Experimental Medicine ◽

10.1084/jem.116.3.295 ◽

1962 ◽

Vol 116 (3) ◽

pp. 295-310 ◽

Cited By ~ 40

Author(s):

G. J. Thorbecke ◽

R. M. Asofsky ◽

G. M. Hochwald ◽

G. W. Siskind

Keyword(s):

Bone Marrow ◽

Antibody Production ◽

Antibody Formation ◽

Gamma Globulin ◽

Short Interval ◽

Secondary Response ◽

White Pulp ◽

Booster Injection ◽

Antibody Formation In Vitro

Antibody formation in vitro by red and white pulp of the spleen and by bone marrow tissue was studied at various days after an intravenous booster injection of soluble antigens such as ovalbumin and bovine gamma globulin (BGG). When the booster injection of antigen was given early (10 days) after an intravenous primary injection, high antibody formation could be demonstrated in the spleen primarily 2 to 3 days after the injection, but much less afterwards. When the booster injection was given later (1 month) after the primary, the antibody production by the spleen lasted longer and higher serum titers were obtained. The bone marrow formed antibody in both cases but, particularly with the short interval between injections, its response was delayed as compared to the spleen. It was also shown that during antibody formation the production of gamma globulin in vitro was enhanced. Histologically the antibody production was always correlated to immature plasma cell proliferation, located at the border of red and white pulp and in the red pulp of the spleen. When endotoxin had been injected at the time of a primary BGG injection, and a second antigen injection was given 5 to 10 days later, a booster response could be elicited which was sometimes limited to the white pulp on day 1, and on day 2 was divided between "red" and "white" pulp. The response induced at day 10, at the peak of secondary nodule proliferation, lasted very long and was accompanied by an enormous plasma cellular proliferation in and around the periarteriolar lymphoid areas of the spleen. The possible importance of the secondary nodules of the white pulp in the preparation for a secondary response is discussed.

Download Full-text