J. M. Khan D.O. H. M. Nasir D.O.1,2, W. M. Ryan III D.O. Larkin Community Hospital, Miami, FL Allergy and Immunology Fellowship Program

1. Immune Response Post-Administration of Polyvalent Pneumococcal Vaccine and Implications
Regarding Clinical Efficacy
J. M. Khan D.O.1,2, H. M. Nasir D.O.1,2, W. M. Ryan III D.O.1,2
1 Larkin Community Hospital, Miami, FL
2 Allergy and Immunology Fellowship Program, Nova Southeastern University College of Osteopathic Medicine, Davie, FL
Introduction
Acknowledgments
Conclusion
Despite low antibody titers post vaccine administration, it may be
possible to confer immunity using pneumococcal vaccine. There
appears to be a decrease in invasive pneumococcal disease post-
vaccine administration, however, there is conflicting data on
whether or not this decreases all-cause mortality, as mentioned.
Further studies are necessary to determine antibody levels for
immunity to each serotype. Other factors would also need further
study in addition to measurement of IgG levels and subtype levels
(IgG1, IgG2, IgG3, and IgG4), including evaluation of opsonization
and phagocytosis involving each specific serotype in both in-vitro
and in-vivo models. In adult populations, additional studies would
also need to be performed to determine the efficacy of use of a
conjugate vaccine as previous studies have shown superior
immunogenicity in pediatric populations.
Methods
Pneumococcal vaccine is FDA approved in adults > 50 and children >
2 at increased risk for developing pneumococcal disease. Due to
multiple serotypes, there is no discrete level for antibody titers which
confer protective immunity. We hypothesize that immunity can be
achieved despite suboptimal antibody response. There are over 90
different capsular serotypes of pneumococcus which have been
identified to date. There are multiple formulations of the
pneumococcal vaccine available, but for the purposes of this
discussion, we focus on 7-valent and 23-valent vaccines (Prevnar and
Pneumovax, respectively), as they have been the most widely studies
to date in both pediatric and adult populations. 7-valent, 10-valent,
and 13-valent vaccines are formulated as conjugate vaccines, whereas
the 23-valent vaccine is not. Currently, the 23-valent vaccine includes
23 purified capsular polysaccharide antigens including serotypes: 1,
2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A,
19F, 20, 22F, 23F, and 33F. These serotypes were chosen to represent
85 to 90 percent of the serotypes that cause invasive disease in the
United States. A 2008 meta-analysis by the Cochrane group that
assessed the efficacy of PPSV23 for preventing pneumococcal
infection in adults had the following findings: strong evidence of
efficacy against IPD (odds ratio 0.26, 95% CI 0.15-0.46),
inconclusive evidence regarding efficacy against all-cause
pneumonia, no reductions in all-cause mortality.1 Immune responses
in immunocomprimised patients vary, and are not included in the
scope of this discussion.
Results
References
Nova Southeastern University- Larkin Community Hospital Program Director:
Shahnaz Fatteh, M.D.
Walter M. Ryan, III, D.O., FAAAAI
We reviewed data from prospective/retrospective studies
evaluating vaccine efficacy. IgM and IgG antibody levels
were measured by ELISA pre and 2-3 weeks post
administration. Incidence of pneumococcal disease was noted
post-vaccine administration. Studies were controlled for
gender, race, and age. Percent response rates were compared
using titers and analyzed in the context of clinical guidelines
suggesting antibody concentration of 1.3 µg/ml or higher or
200 to 300 ng of antibody nitrogen per ml (N/ml-1) per
serotype, a 4-fold rise in antibody titer from baseline, and in
age > 5 years, a response to at least 70% of serotypes. In
patients age 2-5 years, a response to 50% of the capsular
antigens was expected to confer protective immunity.2
Healthy adults were noted to show a 2-fold increase in antibody
titers after vaccination. Higher pre-immunization antibody
concentrations to a specific serotype showed a smaller rise after
immunization. This does not meet clinical criteria for an adequate
immune response. Clinical efficacy studies revealed an
inconsistent relationship between vaccination administration and
subsequent development of pneumococcal disease.
1. Moberley SA, Holden J, Tatham DP, Andrews RM. Vaccines
for preventing pneumococcal infection in adults. Cochrane
Database Syst Rev 2008; :CD000422
2. Sorenson RU, Leiva LE, Giangrosso PA. Response to
heptavalent conjugate Streptococcus pneumoniae vaccine in
children with recurrent infections who are unresponsive to the
polysaccharide vaccine. Pediatr Infect Dis J 1998; 17: 685
3. Jackson LA, Neuzel KM, Yu O. Effectiveness of
pneumococcal polysaccharide vaccine in older adults. NEJM
2003; 348: 18
Disclosures
No financial disclosures to report