Kinetics and Avidity of Antibodies Evoked by Heptavalent Pneumococcal Conjugate Vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

Abstract

The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.

Priming of Immunological Memory by Pneumococcal Conjugate Vaccine in Children Unresponsive to 23-Valent Polysaccharide Pneumococcal Vaccine

“…This better immunogenicity of PCV compared to PPV beyond infancy has also been suggested elsewhere (21,39). Induction of immunological memory after priming with a pneumococcal conjugate vaccine had previously also been shown for infants and patients with HodgkinЈs disease after treatment (9,15). Like in our patients, a marked booster immune response was seen in individuals who initially did not respond to either polysaccharide or conjugate vaccine alone.…”

“…Even for the weak immunogenic serotypes 6B, 18C, and 23F, about two-thirds of our subjects reached this threshold compared to 24%, 53%, and 18%, respectively, in the unprimed group (Table 3). Obviously, the kinetics of pneumococcal antibodies are serotype dependent, an observation also suppported by others (15). As there was only a marginal additional rise in antibody concentrations from day 7 to day 28 in these patients, the IgG antibody peak might have been reached even earlier.…”

Concentration and High Avidity of Pneumococcal Antibodies Persist at Least 4 Years after Immunization with Pneumococcal Conjugate Vaccine in Infancy

“…As reported previously (25), serum IgG antibodies to vaccine serotypes of PCV7 recipients show a response to primary series of three doses, the subsequent decline to the age of 1 year, a strong response to the fourth vaccine dose given at 12 months of age, and again a decline during the next 12 months (Fig. 2).…”

“…The previous data of the FinOM trial for serotypes 6B and 19F show that four doses of PCV7 induce an increase in mean AI between 7 and 24 months for serotype 6B but not for 19F. At the age of 24 months the mean AI is, however, higher in the PCV7 than in the control group for both serotypes (25).…”

“…Serum concentrations of IgG to pneumococcal capsular PSs of vaccine serotypes in samples taken at 2, 4, 6, 7, 12, 13, and 24 months and in the fifth year of life were measured by enzyme immunoassay (EIA), including preadsorption with the cell wall polysaccharide (CPS) but not with type 22F PS (24). The antibody concentrations for vaccine serotypes at 2 to 24 months of age have been described in detail elsewhere (25).…”