Pneumococcal Vaccine

Pneumococcal Vaccine -Summary

• PCV13 is ideal & recommended routinely for all children 2-71 months of age and should be the vaccine of choice in India.

• In healthy children, 6 through 18 years of age PCV13 is now recommended routinely. Children with high risk conditions are eligible for vaccination; and should get a single dose of PCV13.

Pneumococcal Vaccine - Clinical Background

Pneumococcal disease is caused by Streptococcus pneumoniae (pneumococcus). There are over 90 serotypes based on differences in the composition of the polysaccharide capsule that surrounds it. However, the majority of pneumococcal disease in infants is associated with a small number of these serotypes, which may vary by region. Globally, about 20 serotypes are associated with>80% of invasive pneumococcal disease (IPD) worldwide. Invasive pneumococcal infections include pneumonia, meningitis, and febrile bacteremia. It can also lead to otitis media, sinusitis, and bronchitis.

Based on recent estimates, more than 65,000 Indian children died from pneumococcal disease in 2012. Many more were hospitalized. India accounts for 20% of global pneumonia deaths under the age of five. Prior to the use of vaccinations, the World Health Organization (WHO) estimates that 0.7 to 1 million global pneumococcal deaths and 14.5 million global pneumococcal cases per year occurred in children (uninfected with HIV) younger than 5 years.

Rationale for Vaccination

The rationale for childhood immunization is to protect children against life-threatening IPDs such as sepsis, meningitis, and bacteremic pneumonia. Vaccination is the only available tool to prevent pneumococcal disease. The recent development of widespread microbial resistance to essential antibiotics underlines the urgent need for pneumococcal vaccines.

India has thus rolled out the conjugated pneumococcal vaccine (PCV13) as part of the government’s Universal Immunisation Programme (UIP) currently in few states of India.

Historical Background of Pneumococcus Vaccines (PCV7)

The unconjugated pneumococcal vaccine (PPSV23) is poorly immunogenic, has short-lived immunity & is not protective for children younger than 24 months of age. Conjugated vaccines were thus developed for universal childhood immunization of infants and children as early as 6 weeks of age and are now recommended for childhood immunization. The pneumococcal polysaccharide capsular antigens are individually conjugated to a diphtheria membrane carrier protein (CRM197).

The original seven valent conjugated pneumococcal vaccines (PCV7) was produced from the seven most prevalent strains of S. pneumonia in the US. The bacterial capsule sugar was linked to CRM197, a nontoxic recombinant variant of diphtheria toxin. The original 7-valent formulation contained serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. While the proportion of serotypes in children potentially covered by PCV-7 varies markedly from region to region and even from country to country; in most places, at least 50% of invasive isolates from children aged <5 years were represented by PCV-7. It resulted in the protection of 80% of the pneumococcal disease in infants in the US. In Western Europe, at least two-thirds of all isolates were covered by PCV-7. In addition, PCV-7 had a high level of cross-protection against serotype 6A.

The incidence of invasive pneumococcal disease due to vaccine serotypes decreased substantially after the introduction of PCV-7 in the US in vaccinated and unvaccinated children. The largest reductions in IPD incidence were observed in children aged less than 5 years. In addition to the substantial reductions in the incidence of IPD among vaccinated children, the introduction of PCV7 in 2000 also resulted in marked reductions in nasopharyngeal colonization with vaccine serotypes and subsequent reductions in IPD incidence among age groups that were not vaccinated. However, significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period; serotype 19A has become the predominant cause of invasive disease in US children.

In 2010, 13 valent vaccines (PCV13) were introduced which contains six additional strains (i.e., 1, 3, 5, 6A, 19A, and 7F), which protect against the majority of the remaining pneumococcal infections.

Types of Pneumococcal Vaccines

Pneumococcal Conjugate Vaccines (PCV)

Efficacy and Added Benefit of PCV13

Prelicensure studies demonstrated PCV13 to be at least as immunogenic as PCV7 for common serotypes and to induce comparable levels of antibodies for serotypes unique to PCV13. Each of the six new serotypes selected for PCV13 represents a specific target for prevention that is an important cause of ‘epidemic’ IPD on a global basis or has emerged as a frequent cause of invasive disease in at least some of the countries where PCV7 has been introduced (19A, 7F, 3), or represents a cross-reactive serotype that has persisted as a potential cause of IPD (6A) or expanded its role in colonization in children but may not as yet have been demonstrated to be a frequent cause of IPD (6C).

Since the PCV introduction in immunization practice, the incidence of all IPD decreased by 76% in children younger than 5 years, in US. This has also resulted from a reduction in adult cases 65 years and older indicates the significant indirect benefit (Herd immunity) of PCV by interruption of transmission of pneumococci from children to adults.Further pneumococcal disease reductions in children of all ages, have been demonstrated up to this date (CDC data, Redbook, 2015) and the same should be observed in Indian children.

A recent study from India indicated that 73% of the pneumococcal isolates cover PCV13 containing serotypes. (J Infect Dev Ctries. 2013; 7:101-9)

Safety and Efficacy of PCV13

PCV-13 is well tolerated and has a good safety profile. It induces a T-cell dependent immune response characterized by immune memory as well as a booster antibody response on the subsequent challenge with the pneumococcal polysaccharides included in the vaccine. It also stimulates mucosal immunity, resulting in the reduced nasopharyngeal carriage. The herd immunity effect observed with this vaccine is most likely the result of the reduced transmission of vaccine-type pneumococci in the community as a result of decreased carriage.

Non-conjugate Capsular Polysaccharide 23 Valent Vaccine (PPSV23)

It has overall protective efficacy of about 60%-70%. Children under two years of age, and persons suffering from immunodeficiency do not consistently develop immunity following vaccination, thus reducing the protective value of the vaccine in some major target groups for pneumococcal disease. It is meant for high-risk children > 2 years and adults. The PPSV23 protects and covers 10 additional serotypes that are contained in the PCV13 formulation.

Immunization Schedules for PCV vaccines

Indian Academy of Pediatrics Immunization Schedule recommends:

• For routine immunization both PCV10 and PCV13 are licensed for children from 6 weeks to 5 years of age.

• Primary schedule (for both PCV10 and PCV13): 3 primary doses at 6, 10, and 14 weeks with a booster at age 12 through 15 months.

• Additionally, PCV13 is licensed for the prevention of pneumococcal diseases in adults > 50 years of age.

CDC, ACIP Guidelines (North America, Mid East, most Euros’ countries):

• PCV13 is recommended for routine immunization for healthy children at 2, 4, 6, and 12 to 15 months of age.

• Children who miss their shots at these ages should still get the vaccine. The number of doses and the intervals between doses will depend on the child’s age. The recommended Schedule for number of doses of PCV13, including Catch-up immunizations in previously unimmunized and partially immunized children 24-71 months of age are shown in Table 1.

Table 1: PCV doses-schedule, Including Catch-up Immunizations in Previously Unimmunized and Partially Immunized Children

Catch-up Vaccination with PCV13

• Administer 1 dose of PCV13 to all healthy children aged 24 through 71 months who are not completely vaccinated for their age. (Redbook)

• Children with underlying medical conditions younger than 72 months of age who were previously fully immunized with PCV7 should receive one dose of PCV13.

• Older children with immune compromise and other specific high-risk conditions for invasive disease (e.g., cochlear implants, cerebrospinal fluid leaks, hemoglobinopathies, and asplenia) should be immunized with two doses of PCV13 if not previously immunized.

• For high-risk clinical condition, consider 2 doses of PCV13 at least 8 weeks apart if unvaccinated or any incomplete schedule of fewer than 3 doses of PCV that were received previously.

Immunization Schedules for Capsular Polysaccharide Vaccine (PPSV23)

• Not recommended for routine use in infant immunization & healthy individuals (not immunogenic <2 years, T cell independent)

• Recommended only for the vaccination of persons with certain high-risk conditions.

• Single dose for all adults 65 years and older. People with certain chronic health conditions may be recommended to receive a second dose, five years after their first dose.

• If PPSV23 has been received but PCV13 has not, administer 1 dose of PCV13 at least 8 weeks after the most recent dose of PPSV23.

• Vaccination of persons with high-risk conditions: All recommended PCV13 doses should be administered prior to PPSV23 vaccination if possible.

When to Use Combined PCV13 and PPSV23

PPSV23 should never be used alone for prevention of pneumococcal diseases amongst high-risk individuals. Children with the following medical conditions for which PPSV23 and PCV are indicated in the age group 24 through 71 months:

• Children with anatomic or functional asplenia (including sickle cell disease and other hemoglobinopathies, congenital or acquired asplenia, or splenic dysfunction)

• Immune competent children with congenital heart disease (particularly cyanotic type and cardiac failure); chronic lung disease (including asthma if treated with high-dose oral corticosteroid therapy), diabetes mellitus; cerebrospinal fluid leaks; or cochlear implant.

• Children with immune compromising conditions: HIV infection, Nephrotic syndrome and chronic renal failure, diseases associated with treatment with immunosuppressive drugs or radiation therapy, including malignant neoplasms or solid organ transplantation, congenital immunodeficiency.

Immunization in Adults

• One dose of PCV13 is recommended for grown-up children 6 through 18 years of age and adults 19 through 64 years of age with the following medical conditions that put them at high risk for IPD.
  • Functional or anatomic asplenia
  • Congenital or acquired immunodeficiency
  • Nephrotic syndrome
  • Chronic renal failure
  • Chronic lung disease including asthma
  • Cochlear implant(s)
  • Sickle cell disease and other hemoglobinopathies
  • Malignant conditions & long-term immunosuppressive therapy
  • Solid Organ transplant

• Adults 50 years of age or older with one of the above-listed conditions who have not received any pneumococcal vaccine, should get a dose of PCV13 first and a dose of PPSV23 should be given 6 to 12 months later.

• For adults 50 years and older who have already received one or more doses of PPSV23, the dose of PCV13 should be given at least one year after receiving the most recent dose of PPSV23.

  Most healthy adults who get the vaccine develop protection to most or all of these types within two to three weeks of getting the shot. Very old people and people with some long-term illnesses might not respond as well, or at all.

Co-administration with Other Vaccines

• Pneumococcal containing combination (Combo’s) Vaccine are not manufactured and approved for clinical use.

• Concomitant administration of PCV13 and trivalent inactivated influenza vaccine (TIV) has been demonstrated to be immunogenic and safe. The PCV13 can be co-administered with TIV in an adult immunization program.

• Currently, no data are available on co-administration with other vaccines (e.g., tetanus, diphtheria, and acellular pertussis vaccine or zoster vaccine) both among children and adults.

Dosing and Storage

Both PCV vaccines are available as a prefilled syringe and given 0.5 ml intramuscularly. PPSV23 is given subcutaneously. The preferred sites are the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in older children and adults.

Storage:

Precautions and Contraindications

Before administering, vaccination-providers should consult the package insert for precautions, warnings, and contraindications. With PCV (the vaccine recommended for young children) and PPSV (the vaccine for adults and older children), the risk of serious harm is extremely small. Vaccination is contraindicated in persons known to have a severe allergic reaction (e.g., anaphylaxis) to any component of PCV & PPSV23.

The most commonly reported adverse reactions are local reactions of the injection site, pain, redness, or swelling in addition to irritability, decreased appetite, or impaired sleep. Fever may occur within the first 1 to 2 days after injections, particularly after the use of the conjugate vaccine. Other systemic reactions include fatigue, headache, chills, decreased appetite, and generalized muscle pain.