A Primer on Vaccines

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A Primer on Vaccines

Characteristics of a Vaccine

The purpose of a vaccine is to stimulate active immunity and create an immune memory so that exposure to the active disease microorganism will stimulate an already primed immune system to fight the disease. Most vaccines can be divided into the following two types:

Traditionally prepared vaccines are preparations of inactivated (killed) or live attenuated (weakened) bacteria or viruses, parts of the microorganisms, or toxoids (inactivated toxins) from the disease-causing agent. Newer synthetic vaccines use subunit vaccines, conjugate vaccines, and naked DNA vaccines. Critical to the protective effect of subunit vaccines (vaccines consisting of components of the pathogens) are additives called adjuvants, which amplify the immune response. Currently, an aluminum salt-based substance called alum and an oil-based substance called MF59 are two adjuvants licensed for clinical use.

Host Response to Vaccination

Classic preventive vaccines are designed to mimic the effects of natural exposure to microbes. The earliest host response to vaccination is called the innate immune response. This response is an evolutionarily ancient system of host defense that occurs within minutes or hours after vaccination. The dendritic cell is critical to this response. Dendritic cells can sense components of bacteria, viruses, parasites, and fungi through pathogen recognition receptors. One class of these receptors is the toll-like receptor (TLR); at least 10 have been described. As a group, TLRs can sense a wide variety of microbial stimuli (e.g., lipopolysaccharides, viral or bacterial DNA).

The intracellular TLR signaling within dendritic cells is mediated by at least four adapter proteins. Once dendritic cells decode and integrate the signals generated by sensing microbial molecules with TLRs, the cells convey this information to naïve antigen-specific T cells, which launch an immune response.

Over time, vaccine-induced immunity wanes; this may result in increased susceptibility later in life (e.g., varicella [shingles]). A second dose of vaccine could improve protection from primary vaccine failure and waning vaccine-induced immunity.

History of Vaccines

According to the World Health Organization (WHO), immunization is one of the greatest breakthroughs in medical science. This practice saves 3 million lives a year. Vaccines have reduced some preventable infectious diseases to an all-time low; few people now experience the devastating effects of measles, pertussis, and other infectious diseases.

The history of vaccination begins as early as 1000 bce, when the Chinese used smallpox inoculation or variolation, a method of scratching the skin and applying pulverized powder from a smallpox scab. By the 18th century, the practice of variolation became known to Europeans and Americans.

In 1796, Edward Jenner, an English physician, used cowpox scabs to create immunity to smallpox. This was a fundamental principle of immunization, which evolved over 200 years ago and has resulted in the eradication of smallpox globally. The first vaccine for chicken cholera was created in the laboratory of Louis Pasteur in 1879. In 1885, Pasteur developed a rabies vaccine. This launched a period of productive development of many other vaccines (e.g., diphtheria, tetanus, typhoid fever).

Applications of Vaccines

The concept of vaccination, or deliberately introducing a potentially harmful microbe into a patient, initially met with suspicion and outrage. Widespread vaccination programs against contagious infectious diseases now have a positive influence worldwide.

In 1721, Cotton Mather, a Boston minister, encouraged smallpox variolation as a preventive step subsequent to the Boston smallpox epidemic. Mather was widely criticized by suspicious citizens for his role in promoting variolation. Since the introduction of the first vaccine, there has been opposition to vaccination. In 1910, Sir William Osler expressed his frustration with the antivaccinationist movement. Although fear and mistrust have arisen every time a new vaccine was introduced in the 18th century, the antivaccine movement receded between the 1940s and the early 1980s. Three trends promoted a positive attitude toward vaccines:

An increase in antivaccinationist thinking emerged in the 1970s, when outbreaks of infectious diseases decreased, with more vaccines in the childhood vaccination schedule. When countries dropped pertussis vaccination from the vaccination schedule, the incidence of whooping cough increased 10 to 100 times. Fears grew in the late 1990s, when vaccines were suspected of causing autism. Once again, in 2009 and 2010, the H1N1 influenza pandemic evoked strong public fear of vaccination. Reemergence of a previously controlled disease, such as pertussis, has led to hospitalizations and deaths. The worst pertussis outbreaks in the past 50 years are now occurring in California.

Despite public fears, American children now receive vaccinations to numerous diseases that were once common childhood infectious diseases. In the United States, the recommended childhood immunization schedule now includes vaccines to protect against 15 diseases, including seasonal influenza. Immunization schedules vary by age and by country (Tables 16-1 to 16-3, A and B).

Table 16-1

Childhood Vaccination Schedule, South Africa, 2011

Age Vaccine (No. of Doses)
At birth BCG, vaccine against tuberculosis; trivalent oral polio vaccine (TOPV)
6 wk TOPV (one); rotavirus vaccine (RV) oral (one); DTaP-IPV/Hib vaccine (one); hepatitis B vaccine (one); PCV7 pneumococcal vaccine (one)
10 wk DTaP-IPV/Hib vaccine (two); DTaP (two); hepatitis B vaccine (two)
14 wk RV, oral rotavirus vaccine (two); DTaP-IPV/Hib vaccine (three); hepatitis B vaccine (three); PCV7, pneumococcal vaccine (two)
9 mo Measles vaccine (one); PCV7, pneumococcal vaccine (three)
18 mo DTaP-IPV/Hib vaccine (four); measles vaccine (two)
6 yr Td vaccine
12 yr Td vaccine

BCG, Bacillus Calmette-Guérin; DTaP-IPV/Hib, Diphtheria and tetanus toxoids and acellular pertussis vaccine; Hib, Haemophilus influenzae type b, tetanus; IPV, inactivated polio vaccine; Td, vaccine against tetanus (lockjaw) with reduced strength of diphtheria.

From South African Vaccination and Immunisation Centre: www.savic.ac.za.

Table 16-2

Recommended Immunizations for Children, Birth Through 6 Years Old, United States, 2011

Age Vaccine
Birth Hepatitis B (HepB) 11
1 mo HepB 22
2 mo HepB 2, if not given at 1 mo; rotavirus vaccine (RV)2; diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP)3; Haemophilus influenzae type b conjugate vaccine (Hib)4; pneumococcal vaccine (PCV)5; inactivated poliovirus vaccine (IPV)6
4 mo RV2; DTaP3; Hib4; PCV5; IPV6
6 mo HepB 3 (6-18 mo)1; RV2; DTaP3; Hib4; PCV5; IPV (6-18 mo)6; influenza yearly7 (6 mo-6 yr)
12 mo Hib4; PCV5; measles, mumps, and rubella (MMR) (12-15 mo)8; varicella (12-15 mo)9; hepatitis A (HepA)10 (12-23 mo); second dose should be given 6-18 mo later
15 mo DTaP3
18 mo Influenza yearly7
2-3 yr Influenza yearly7
4-6 yr Influenza yearly7; DTaP3; IPV6; MMR8; varicella9

Note: Meningococcal conjugate vaccine, quadrivalent (MCV4), minimum age, 2 yr.

1Hepatitis B vaccine (HepB) (minimum age, birth).

At birth:

Doses following the birth dose:

2

3Diptheria and tetanus toxides and acellular perfusion vaccine (DTaP) (minimum age, 6 wk).

4Hemophilus influenzae type b-conjugate vaccine (Hib) (minimum age, 6 wk).

5Pneumococcal vaccine (minimum age, 6 wk for pneumococcal conjugate vaccine [PCV]; 2 yr for pneumococcal polysaccharide vaccine [PPSV]).

PCV is recommended for all children <5 yr. Administer one dose of PCV to all healthy children aged 24-59 mo who are not completely vaccinated for their age.

A PCV series begun with 7-valent PCV (PCV7) should be completed with 13-valent PCV (PCV13).

A single supplemental dose of PCV13 is recommended for all children aged 14-59 mo who have received an age-appropriate series of PCV7.

A single supplemental dose of PCV13 is recommended for all children aged 60-71 mo with underlying medical conditions who have received an age-appropriate series of PCV7.

The supplemental dose of PCV13 should be administered at least 8 wk after the previous dose of PCV7. See MMWR 2010:59(No. RR-11).

Administer PPSV at least 8 wk after last dose of PCV to children aged 2 yr or older with certain underlying medical conditions, including a cochlear implant.

6Inactivated poliovirus vaccine (IPV) (minimum age, 6 wk).

7Influenza vaccine (seasonal); (minimum age, 6 mo for trivalent inactivated influenza vaccine [TIV]; 2 yr for live attenuated influenza vaccine [LAIV]).

8Measles, mumps, and rubella vaccine (MMR) (minimum age, 12 mo). See MMWR 2010;59(No. RR-8):33–34.

9Varicella vaccine (minimum age, 12 mo).

10Hepatitis A vaccine (HepA) (minimum age, 12 mo).

Administer two doses at least 6 mo apart.

HepA is recommended for children >23 mo who live in areas in which vaccination programs target older children, who are at increased risk for infection, or for whom immunity against hepatitis A is desired.

From Centers for Disease Control: www.cdc.gov/vaccines

Immunization Schedules (www.cdc.gov/vaccines) Retrieved October 31, 2011.

Centers for Disease Control: ___________Prevention of Pneumococcal Disease Among Infants and Children — Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine

December 10, 2010 / 59(RR11);1-18 MMWR Morb Mortal Wkly Rep 59(RR-11) 2010; and

Prevention and Control of Influenza with Vaccines

Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010

August 6, 2010 / 59(rr08);1-62 Centers for Disease Control: MMWR Morb Mortal Wkly Rep 59(RR-8):33–34, 2010.

Table 16-3A

Recommended Immunization Schedule for Persons 7-18 years, United States, 2011

Vaccine Age (yr)
7-10 11-12 13-16
Tetanus, diphtheria, pertussis (Tdap)1 1 dose, if indicated Tdap1 Tdap1
Human papillomavirus (HPV)2 See footnote.2 3 doses Complete 3-dose series
Meningococcal (MCV4)3 See footnote.3 1 dose MCV43

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1Tetanus and diphtheria toxoids and acellular pertussis vaccine (Tdap, minimum age, 10 yr for Boostrix and 11 yr for Adacel).

2Human papillomavirus (HPV) vaccine. HPV4 (Gardasil) and HPV2 (Cervarix). (minimum age, 9 yr).

3Meningococcal conjugate vaccine/MCV4, quadrivalent (minimum age, 2 yr).

• Administer MCV4 at age 11-12 yr with a booster dose at age 16 yr.

• Administer one dose at age 13-18 yr if not previously vaccinated.

• Persons who received first dose at age 13-15 yr should receive a booster dose at age 16-18 yr with a minimum interval of at least 8 wk after the preceding dose.

• If the first dose is administered at age 16 yr or older, a booster dose is not needed.

• Administer two doses at least 8 wk apart to previously unvaccinated persons with persistent complement component deficiency and anatomic or functional asplenia, and one dose every 5 yr thereafter.

• Adolescents aged 11-18 with human immunodeficiency virus (HIV) infection should receive a two-dose primary series of MCV4, at least 8 wk apart.

• See MMWR 2011;60:72-76, available at http://www.cdc.gov/mmwr/pdf/wk/mm6003.pdf and Vaccines for Children Program.

Reference: www.cdc.gov/vaccines, retrieved October 1, 2012.

From Centers for Disease Control: Vaccines and immunizations, 2012 (www.cdc.gov/vaccines).

Table 16-3B

Recommended Immunization Schedule for Persons aged 7-18 years, United States, 2012

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Vaccine Age: 7-18 yr
Influenza4 Yearly for all children
Pneumococcal (PCV13)5 See footnote.5
Hepatitis A (Hep A)6 Complete 2-dose series
Hepatitis (Hep B)7 Complete 3-dose series