Safety and Immunogenicity of 23-valent Pneumococcal Polysaccharide Vaccine in 2 to 70 Years Old Healthy People in China
Safety and Immunogenicity of 23-valent Pneumococcal Polysaccharide Vaccine in 2 to 70 Years Old Healthy People in China
Pneumococcal infection is a leading cause of death throughout the world and a major cause of
 pneumonia, bacteremia, meningitis, and otitis media.

 It has been established that purified pneumococcal capsular polysaccharides induce antibody
 production and such antibody is effective in preventing pneumococcal disease. Clinical
 studies have demonstrated the immunogenicity of each of the 23 capsular types when tested in
 polyvalent vaccines. Studies of 23-valent pneumococcal vaccine in children of two years old
 and older and in adults of all ages have showed immunogenic response. In order to provide
 more evidence for the immunogenicity and the safety of the vaccine, a phase III clinical
 trial is planed to conduct.
Pneumonia is a major cause of morbidity and mortality in developing countries. Pneumonia is
 predominantly bacterial in origin: isolation rates of Streptococcus pneumoniae and
 Haemophilus influenzae were 34% and 40%, respectively, in a series of lung aspirates
 collected from children under 5 years of age (Shann et al., 1984).

 Pneumococcal infection is a leading cause of death throughout the world and a major cause of
 pneumonia, bacteremia, meningitis, and otitis media.

 Strains of drug-resistant S. pneumoniae have become increasingly common in China and in other
 parts of the world. In some areas as many as 35% of pneumococcal isolates have been reported
 to be resistant to penicillin. Many penicillin-resistant pneumococci are also resistant to
 other antimicrobial drugs (e.g., erythromycin, trimethoprim-sulfamethoxazole and
 extended-spectrum cephalosporins), therefore the importance of vaccine prophylaxis should be
 emphasized against pneumococcal disease.

 Epidemiology Pneumococcal infection causes approximately125,000 deaths annually in China. At
 least 2,500,000 cases of pneumococcal pneumonia are estimated to occur annually in the United
 States; S. pneumoniae accounts for approximately 25-35% of cases of community-acquired
 bacterial pneumonia in persons who require hospitalization.

 Despite appropriate antimicrobial therapy and intensive medical care, the overall
 case-fatality rate for pneumococcal bacteremia is 15-20% among adults, and among elderly
 patients this rate is approximately 30-40%. An overall case-fatality rate of 36% was
 documented for adult inner-city residents who were hospitalized for pneumococcal bacteremia.

 Invasive pneumococcal disease (e.g., bacteremia or meningitis) and pneumonia cause high
 morbidity and mortality in spite of effective antimicrobial control by antibiotics. These
 effects of pneumococcal disease appear due to irreversible physiologic damage caused by the
 bacteria during the first 5 days following onset of illness, and occur regardless of
 antimicrobial therapy. Vaccination offers an effective mean of further reducing the mortality
 and morbidity of this disease.

 Risk Factors In addition to the very young and persons 65 years of age or older, patients
 with certain chronic conditions are at increased risk of developing pneumococcal infection
 and severe pneumococcal illness.

 Patients with chronic cardiovascular diseases (e.g., congestive heart failure or
 cardiomyopathy), chronic pulmonary diseases (e.g., chronic obstructive pulmonary disease or
 emphysema), or chronic liver diseases (e.g., cirrhosis), diabetes mellitus, alcoholism or
 asthma (when it occurs with chronic bronchitis, emphysema, or long-term use of systemic
 corticosteroids) have an increased risk of pneumococcal disease. In adults, this population
 is generally immunocompetent.

 Patients at high risk are those who have a decreased responsiveness to polysaccharide antigen
 or an increased rate of decline in serum antibody concentration as a result of:
 immunosuppressive conditions (congenital immunodeficiency, human immunodeficiency virus (HIV)
 infection, leukemia, lymphoma, multiple myeloma, Hodgkin's disease, or generalized
 malignancy); organ or bone marrow transplantation; therapy with alkylating agents,
 antimetabolites, or systemic corticosteroids; chronic renal failure or nephrotic syndrome.

 Patients at the highest risk of pneumococcal infection are those with functional or anatomic
 asplenia (e.g., sickle cell disease or splenectomy), because this condition leads to reduced
 clearance of encapsulated bacteria from the bloodstream. Children who have sickle cell
 disease or have had a splenectomy are at increased risk of outbreak pneumococcal sepsis
 associated with high mortality.

 Immunogenicity It has been established that purified pneumococcal capsular polysaccharides
 induce antibody production and that such antibody is effective in preventing pneumococcal
 disease. Clinical studies have demonstrated the immunogenicity of each of the 23 capsular
 types when tested in polyvalent vaccines.

 Studies of 23-valent pneumococcal vaccines in children of two years old and older and in
 adults of all ages have showed immunogenic responses. Protective capsular type-specific
 antibody levels generally develop in the third week following vaccination.
Inclusion Criteria:

 -  Aged 2 to 70 years on the day of inclusion

 -  Informed consent form signed by subjects and parent/guardian

 -  Subjects and parents/guardians able to attend all scheduled visits and comply with all
 study procedures

 Exclusion Criteria:

 -  Subjects with any pneumococcal vaccine before vaccination

 -  History of pneumococcal infection

 -  Women in pregnancy or lactation period in trial period

 -  Allergic history or any SAE after vaccination, such as allergy, urticaria, dyspnea,
 angioedema, celialgia

 -  Known or suspected immune dysfunction, including persons with congenital
 immunodeficiency or persons with HIV positive.

 -  Functional or anatomic asplenia

 -  Patients treated with chemotherapy in past 5 years or administered with
 immunosuppressive agents, cytotoxicity factor or corticosteroids in the 6 months
 preceding the vaccine trial

 -  Receipt of blood or blood-derived products in the 3 months preceding vaccination

 -  Participation in another clinical study investigating a vaccine, drug in the 30 days
 preceding vaccination

 -  Receipt of any live virus vaccine in the 30 days preceding vaccination

 -  Receipt of any subunit vaccine and inactivated vaccine in the 14 days before
 vaccination

 -  Thrombocytopenia, bleeding disorder

 -  History of asthma，angioneurotic edema，diabetes mellitus or malignancy tumor

 -  History of thyroid gland excision or treatment for thyroid gland disease in last 12
 months

 -  Hypertension, blood pressure still above 145/95mmHg even with drug treatment

 -  History of eclampsia, epilepsia, psychosis

 -  Febrile illness (temperature ≥ 38°C) in the 3 days or any acute illness/infection in
 the 7 days preceding vaccination

 -  In progress of anti-tuberculosis prophylaxis or therapy

 -  Those can not fulfill the protocol or can not sign the informed consent form for any
 medical, psychological, social, occupational and other reasons, according to
 investigator judgment