Heptavalent pneumococcal conjugate vaccine

Based on the differences in pneumococcal capsular polysaccharide antigens, more than 90 serotypes can be identified, and the distribution of pathogenic serotypes varies at different ages and geographical locations. The serotype coverage of this vaccine in the United States is between 89% and 93%, and clinical effectiveness evaluation for invasive disease (IPD) has been obtained in the American population. Epidemiological research data from 1988 to 2003 showed that the coverage of this product in Europe was low and varied between different countries and regions. In European children under 2 years old, this vaccine can cover 71% to 86% of the serotypes of pneumococcal invasive disease (IPD) isolates and more than 80% of the serotypes of antibiotic-resistant strains. Vaccine serotype coverage in the pediatric population decreases with age. In European children aged 2 to 5 years, this vaccine can cover approximately 50%-75% of clinical isolates that cause invasive pneumococcal disease. The reduction in the incidence of IPD seen in older children may be partly due to naturally acquired immunity. At present, my country lacks epidemiological data on invasive diseases and related serotypes caused by Streptococcus pneumoniae in recent years, and it is still unclear what serotype coverage this product has for invasive diseases caused by pneumococcus in my country. 1. Foreign clinical studies on the effectiveness of preventing invasive diseases In 1995, a large-scale randomized double-blind clinical trial (NCKP) involving a multi-ethnic population in California, North America evaluated the effectiveness of this product in preventing invasive diseases. More than 37,816 infants were vaccinated with this vaccine or a control vaccine (meningococcal conjugate vaccine type C) at 2, 4, 6, and 12 to 15 months of age. During the trial, the serotypes included in the vaccine accounted for 89% of the IPD. As of 1999, during the blind follow-up period, there were a total of 52 cases of invasive diseases caused by the serotypes of this vaccine (all with bacteremia, and some meningitis and pneumonia), 3 cases in the ITT population test group, and 49 cases in the control group. The serotype-specific vaccine efficacy was evaluated in the ITT population and was 94% (95% CI: 81, 99) and 97% (95% CI: 85, 100) in the PP population. In Europe, considering the impact of this product on the coverage of serotypes that cause invasive diseases, the vaccine effectiveness is between 65% and 79%. In the NCKP trial, the effectiveness of the vaccine against bacteremic pneumonia caused by serotypes of pneumococci covered by the vaccine was 87% (95% CI: 799). The antibodies produced by the immunogenic vaccine against each serotype-specific capsular polysaccharide are considered to be protective against invasive diseases. However, the minimum protective antibody concentration for each serotype of invasive disease has not yet been determined. WHO recommends that the antibody concentration for all pneumococcal serotypes is ge; 0.35mu; g/ml, which can predict the vaccine's effectiveness in preventing invasive pneumococcal disease. In foreign countries, in infants/young children who have received 4 or 3 doses of this vaccine, although the geometric mean concentrations between serotypes are different, significant antibody responses can be seen for all serotypes. All serotypes can see the peak response of basic immunity after 3 doses, and can see the booster after the 4th dose. The results of the opsonophagocytosis test after basic immunization showed that this vaccine induces functional antibodies to all vaccine serotypes. No clinical study has been conducted on the persistence of antibodies after infants and older children have completed immunization (boosting immunization). In foreign clinical trials, the use of simple polysaccharide vaccines (such as 23-valent pneumococcal polysaccharide vaccine) 13 months after the basic immunization of this vaccine can also induce immune memory responses to 7 serotypes. 2. Domestic clinical trials In China, this product has been clinically tested for immunogenicity (basic immunization and boosting immunization) and safety in infants aged 3 to 5 months, and clinical studies on its effectiveness in preventing invasive diseases have not yet been conducted. Immunogenicity was evaluated in an open, randomized, controlled study conducted on healthy infants in China. Three doses of basic immunization were administered separately or simultaneously with DTaP at 3, 4, and 5 months of age, and the control group was only vaccinated with DTaP. One month after the third dose, the geometric mean concentration (GMC) of serum specific antibodies in subjects vaccinated with this vaccine increased and was significantly higher than that in the control group. The GMC of subjects vaccinated separately from DTaP ranged from 3.10mu;g/ml (serotype 6B) to 17.75mu;g/ml (serotype 14). The proportion of subjects with antibody concentration ge;0.35mu;g/ml ranged from 87.88% (serotype 6B) to 100% (serotypes 4, 9V, 14, 18C). In the control group, only 27.66% of the subjects had serotype 14 antibody concentration ge;0.35mu;g/ml, while the proportion of other serotype antibodies reaching this level was less than 10%. The results of the study suggest that this product can induce a good immune response in Chinese infants when vaccinated separately from DTaP at 3, 4, and 5 months of age. See the table below for details: The proportion of subjects with antibody concentration ge;0.35mu;g/ml before and after primary immunization in the two groups. The two groups of subjects (60 and 61, respectively) who received this product in the primary immunization study phase received the fourth booster immunization at 12 to 15 months of age and showed obvious booster immunization responses. After booster immunization, the GMC increase of subjects who received this product and DTaP separately in the primary immunization phase ranged from 5.13 (serotype 14) to 18.46 (serotype 23F), and the GMC increase of subjects who received this product and DTaP simultaneously in the primary immunization phase ranged from 9.43 (serotype 14) to 27.46 (serotype 23F). The GMC increase of each serotype in the two groups (after vaccination/before vaccination) was statistically significant (p0.0001). The results of the study suggest that this product can effectively induce immune memory responses in Chinese infants.

Each 0.5ml dose of this vaccine contains 16μg of various types of polysaccharides (total amount of polysaccharides): 4μg of type 6B, 2μg of types 4, 9V, 14, 18C, 19F and 23F respectively; each type of polysaccharide is combined with CRM197 carrier protein and adsorbed on aluminum phosphate adjuvant (0.5mg). It also contains sodium chloride and water for injection.

1. This product is used for infants aged 3 months to 2 years, and children aged 2 years to 5 years who have not been vaccinated with this vaccine (please refer to [Precautions] for high-risk groups). Recommended routine immunization program: basic immunization at 3, 4, and 5 months of age, and booster immunization at 12 to 15 months of age. 2. This product is used for active immunization of infants and young children to prevent invasive diseases caused by the 7 serotypes of pneumococci included in this vaccine (4, 6B, 9V, 14, 18C, 19F and 23F). Pneumococcus is a common cause of invasive infections (including sepsis, meningitis, bacteremic pneumonia and bacteremia), as well as upper respiratory tract infections such as pneumonia. Infants and young children under 2 years old are at the highest risk of invasive diseases. 3. The use of this vaccine should take into account the differences in the serotypes of pneumococcal diseases caused by different regions and the impact of invasive diseases on different age groups. This vaccine does not prevent infections caused by other types of pneumococci other than the serotypes included in the vaccine, nor does it prevent invasive infections caused by other microorganisms.

This vaccine should be shaken well before use and is for intramuscular injection only. The preferred site is the anterolateral thigh area (vastus lateralis) of infants or the deltoid muscle of the upper arm of children. The intramuscular injection dose is 0.5 ml. Be careful not to inject into the adjacent nerves and blood vessels. The vaccine cannot be injected into the buttocks. This product is approved in the United States and Europe for simultaneous vaccination with other childhood vaccines (DTwP, DTaP, Hib, IPV, OPV, hepatitis B vaccine, MMR, varicella vaccine). However, it is not recommended to vaccinate this vaccine with other children's immunization vaccines or routine children's vaccines in China at present. Infants aged 3 to 6 months: 3 doses of basic immunization, 0.5 ml each; the first vaccination is at 3 months of age, and the immunization program is one dose each at 3, 4, and 5 months of age, with at least 1 month between each vaccination. It is recommended to vaccinate the fourth dose at 12 to 15 months of age. Infants and children who have not been vaccinated with this vaccine (based on foreign immunogenicity and safety clinical trials): Infants aged 7 to 11 months: 2 doses of basic immunization, 0.5 ml each, with at least 1 month between each vaccination. It is recommended that the third dose be given after 12 months of age, with at least a 2-month interval between the second dose and the third dose. Children aged 12 to 23 months: 2 doses, 0.5 ml each, with at least a 2-month interval between each dose. Children aged 24 months to 5 years: 1 dose.

1. Abroad Clinical Adverse Reactions This product has been studied in several controlled clinical studies on more than 18,000 healthy infants (6 weeks to 18 months) abroad to evaluate the safety of this vaccine. The vast majority of the following safety results are mainly from 17,066 infants who received a total of 55,352 doses of this product in the clinical efficacy trial (NCKP). In addition, safety assessments were conducted on older children who had not been immunized with this vaccine. In all clinical trials, this vaccine was administered in combination with other recommended childhood vaccines, and the most common adverse reactions were local adverse reactions at the injection site and fever. During basic immunization or booster immunization, repeated vaccinations did not result in a sustained increase in local or systemic adverse reactions. For children aged 2 to 5 years using a single-dose immunization regimen, the incidence of local adverse reactions was higher than that of infants, and they were mainly transient reactions. Adverse reactions reported in clinical trials of all age groups or from post-marketing experience with this product are listed below in descending order of severity, classified by body organ category and incidence. According to the classification of CIOMS adverse reaction incidence: very common (ge; 10%); common (ge; 1% and 10%); occasional (ge; 0.1% and 1%); rare (ge; 0.01% and 0.1%); very rare (0.01%). Adverse reactions of various body systems Local reactions at the injection site Very common: redness, induration/swelling, pain/tenderness at the injection site Common: induration/swelling or erythema with a diameter greater than 2.4 cm, pain/tenderness that interferes with movement Digestive system Very common: diarrhea, vomiting Systemic reactions Very common: fever Common: fever above 39°C Metabolic and nutritional disorders Very common: loss of appetite Nervous system Very common: fatigue, sleep disruption Rare: convulsions (including febrile convulsions), hypotonia-hyporesponsiveness episodes Psychiatric system Very common: irritability Skin and subcutaneous tissue reactions Rare: dermatitis at the injection site, urticaria and itching at the injection site Other adverse reactions after overseas marketing: Such incidence is based on spontaneous reporting rates and is calculated using the number of reports and the number of doses sold. Uncommon: rash, urticaria or urticarial rash Blood and lymphatic system Very rare: lymphadenitis limited to the injection site Immune system reactions Rare: allergic/anaphylactoid reactions including shock, angioedema, dyspnea, bronchospasm, facial edema Skin and subcutaneous tissue reactions Very rare: erythema multiforme Psychiatric system Very common: crying As with other vaccines used in childhood, spontaneous reports of apnea have been reported with this product, which is temporally related to the administration of this vaccine. Most cases were given at the same time as other vaccines, including diphtheria-tetanus-pertussis vaccine (DTP), diphtheria-tetanus-acellular pertussis vaccine (DTaP), hepatitis B vaccine, inactivated poliovirus vaccine (IPV), Haemophilus influenzae b vaccine (Hib), measles-mumps-rubella vaccine (MMR) and/or varicella vaccine, but in most reports, there was an underlying disease such as apnea, infection, prematurity and/or a history of seizures. An infant surveillance study reported an increased risk of hospitalization for wheezing in infants vaccinated with this vaccine compared with historical controls. Due to confounding factors such as concurrent vaccination with alternative vaccines, annual variations in respiratory syncytial virus (RSV) or influenza virus infection, and increasing trends in respiratory disease, other analyses in this study and long-term follow-up analyses of key large-scale, multicenter, controlled effectiveness studies have not been able to confirm that this phenomenon is related to this product. 2. Domestic clinical adverse reactions A total of 592 subjects were vaccinated with this product in the domestic registered clinical trials. The safety information after combined analysis of local reactions, systemic reactions and adverse events related to this vaccine is summarized as follows: When this vaccine was administered separately from DTaP (297 cases), the most common systemic adverse reactions were fever (37.5℃) and sleep interruption (26.60%), irritability (21.89%), decreased appetite (15.49%) and diarrhea (14.81%). Most symptoms were mild, and 2 cases (0.79%) had a body temperature of 39℃; local adverse reactions at the injection site included erythema (11.11%), nodules (7.74%) and pain (9.09%), and erythema and nodules with a diameter of 2.5 cm accounted for 1%. The incidence of the above adverse reactions was highest after the first dose, and decreased to varying degrees after the second and third doses. When this vaccine was administered simultaneously with DTaP (295 cases), the most common systemic adverse reactions were fever (37.5℃) (28.81%), sleep interruption (26.78%), irritability (26.44%), diarrhea (24.07%), and decreased appetite (16.61%). Most symptoms were mild, with 4 cases (1.36%) experiencing a body temperature of 39℃. Local adverse reactions at the injection site included erythema (10.85%), nodules (7.46%), and pain (11.86%), with erythema and nodules with a diameter of 2.5 cm accounting for 1%. The above adverse reactions also had the highest incidence after the first dose, and decreased to varying degrees after the second and third doses. The above clinical trials did not find adverse events not listed in the foreign instructions. Common adverse reactions are basically consistent with the safety information in the foreign instructions.

This vaccine is contraindicated for patients who are allergic to any ingredient in it or to diphtheria toxoid.

This product is approved in the United States and Europe for simultaneous administration with other childhood vaccines (DTwP, DTaP, Hib, IPV, OPV, hepatitis B vaccine, MMR, varicella vaccine). During clinical studies, vaccines administered simultaneously with this vaccine include diphtheria, tetanus, pertussis vaccine (DTP) or diphtheria, tetanus, acellular pertussis vaccine (DTaP), Haemophilus influenzae type b (Hib), oral polio vaccine (OPV) or inactivated polio vaccine (IPV), hepatitis B vaccine, meningococcal serogroup C conjugate vaccine, measles-mumps-rubella vaccine (MMR) and varicella vaccine. Therefore, the safety experience of this vaccine indicates that this vaccine can be included in the routine immunization program. In some studies, the differences in antibody responses to certain antigens have different results, but these differences are not expected to have any clinical significance. However, it is not recommended to administer this vaccine simultaneously with other childhood immunization vaccines or routine childhood vaccines in China at present.

Store in a refrigerator (2℃-8℃). This vaccine should not be frozen. If the vaccine has been frozen, it should be discarded and cannot be used again. Please keep this product out of the reach of children.

0.5ml/vial

48 months.