Contents

1 General immunisation principles

1.1 Immunity and immunisation

Immunity is the biological state of being able to protect oneself from infection and disease. The immune system is a complex network of organs, cells and molecules interacting with the rest of the body as well as the environment. It includes innate (non-specific, non-adaptive) mechanisms and acquired (specific, adaptive) systems.

One of the immune system’s primary functions is to identify and remove infectious organisms, thereby preventing disease. It does this by recognising molecular fragments of microbes, called antigens. Immunity can be achieved either actively, by exposure to the disease or vaccination, or passively via antibody transfer in utero and through breast milk, or by injecting serum that contains antibodies.

The essential goal of active immunisation is to prime and prepare the immune system so that it can respond rapidly and specifically to the wild organism, thereby preventing (or attenuating) disease and, ideally, colonisation and infection.

1.1.1 Disease transmission, herd immunity and immunisation coverage

Vaccines are given to people to protect them against disease. They provide not only individual protection for some diseases but also population-wide protection by reducing the incidence of diseases and preventing them spreading to vulnerable people. Some of these population-wide benefits only arise with high immunisation rates, depending on the infectiousness of the disease and the effectiveness of the vaccine.

The basic reproduction number (R0) is the number of secondary cases generated by a typical infectious individual when the rest of the population is susceptible. In other words, R0 describes the spreading potential of an infection in a population.1 Measles is one of the most infectious diseases, with an R0 of 12–18 (Table 1.1). In other words, one person with measles is likely to infect up to 18 other people.

If a significant proportion of the population are immune, then the chain of disease transmission is likely to be disrupted. This is called herd immunity. The herd immunity threshold (H) is the proportion of immune individuals in a population that must be exceeded to prevent disease transmission. For example, to prevent measles transmission, 92–94 percent of the population must be immune (Table 1.1).

R0 must remain above 1 in order for an infection to continue to exist. Once R0 drops below 1 (such as in the presence of an effective vaccination programme), the disease can be eradicated. The greater the proportion of the population that is immune to the infection, the lower the R0 will be. For example, data from an Australian study2 indicates that an HPV (human papillomavirus) vaccine programme with 70 percent coverage in young women may lead to the near disappearance of genital warts from the heterosexual population, and the authors suggest that the R0 for HPV types 6 and 11 (causing genital warts) has fallen to below 1 (see the herd immunity discussion in section 9.4.2).

Table 1.1: Approximate basic reproduction numbers (in developed countries) and implied crude herd immunity thresholdsa for common vaccine-preventable diseasesb

Infection Basic reproduction number (R0) Crude herd immunity threshold, H (%)
Diphtheria 6–7 83–85
Influenzac 1.4–4 30–75
Measlesd 12–18 92–94
Mumps 4–7 75–86
Pertussis 5–17 92–94
Polioe 2–20 50–95
Rubella 6–7 83–85
Smallpox 5–7 80–85
Tetanus Not applicable Not applicable
Tuberculosis Not defined Not defined
Varicella 8–10 Not defined

Notes

a The herd immunity threshold (H) is calculated as 1−1/R0.
b The values given in this table are approximate: they do not properly reflect the tremendous range and diversity among populations, nor do they reflect the full immunological complexity underlying the epidemiology and persistence of these infections.
c The R0 of influenza viruses probably varies greatly among subtypes.
d Herd immunity thresholds as low as 55% have been published.
e This is complicated by uncertainties over immunity to infection and variation related to hygiene standards.

Source: Adapted from Fine PEM, Mulholland K. 2013. Community immunity. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines. Elsevier Saunders. Table 71.2.

Immunisation coverage

High immunisation coverage is important to protect not only the health of an individual but, for most vaccines, the health of the community as well. High coverage reduces the spread of disease to those who have not been vaccinated because of medical reasons (eg, children with leukaemia while receiving treatment), or because of age (eg, infants who are too young to respond to some vaccines).

New Zealand’s target for immunisation coverage is for at least 95 percent of children to be fully immunised by age 8 months, and then at age 2 years. This target is based on the need for:

For the three months ending 31 December 2015, 93.7 percent of New Zealand children were fully immunised by age 8 months and 93.2 percent were fully immunised by age 2 years. National and DHB immunisation coverage data is available on the Ministry of Health website (www.health.govt.nz/our-work/preventative-health-wellness/immunisation/immunisation-coverage/national-and-dhb-immunisation-data).

1.1.2 Innate and specific immunityTop

Innate immunity

Most infectious microbes (also known as micro-organisms) are prevented from entering the body by barriers such as skin, mucosa, cilia and a range of anti-microbial enzymes. Any microbes that breach these surface barriers are then attacked by other components of the innate immune system, such as polymorphonuclear leucocytes (neutrophils), macrophages and complement.

The cells and proteins of the innate immune system are able to recognise common microbial fragments and can kill microbes without the need for prior exposure. The cells of the innate immune system also interact with the cells of the adaptive immune system (eg, lymphocytes) to induce a cascade of events that results in the development of specific immunity and immune memory.

Specific immunity

B lymphocytes (B cells) and T lymphocytes (T cells), which come in a range of subsets with different functions, are responsible for specific immune responses. Plasma cells, a subset of B cells, secrete antibodies that play a vital role in killing microbes, such as viruses and bacteria, and inactivating toxins. Memory B cells are long lived and if stimulated by re-exposure to a microbial antigen can rapidly proliferate and secrete large amounts of antibody long after the original infection or vaccination has occurred.

Some T lymphocyte subgroups, such as T helper lymphocytes, have a role in directing the specific immune response, while others, such as cytotoxic T lymphocytes, have a role in killing pathogens, either directly or by killing host cells that have become infected. Another subset of T cells reside as memory T cells and can also be reactivated upon repeat exposure.

Vaccine-induced immunity follows a similar process, with the development of specific immunity and memory, but it is designed to produce maximal protective immunity with minimal systemic or local reactions.

1.1.3 Active and passive immunityTop

Active immunity

Active immunity is generated by the host’s specific immune system, following exposure either to a microbe or to a microbial antigen (such as a surface protein or toxin).

The primary immune response, following first exposure to a microbe or antigen, is evidenced by plasma cells secreting first immunoglobulin M (IgM) and then immunoglobulin G (IgG). This first response is slow and peaks after around 30 days. The secondary immune response, which follows subsequent exposure to the same microbe or antigen, results in a more rapid response by plasma cells, which secrete very large amounts of IgG highly specific to the microbe or antigen. The secondary response peaks in four to seven days. Although the T-cell responses are also important for protection, it is usually the level of antibodies directed against a microbe or antigen that is measured in order to quantify an immune response.

Passive immunity

Passive immunity does not depend on the recipient’s immune response for protection and is only temporary, lasting weeks to months. Passive immunity can be provided by the injection of human immunoglobulin, which is derived from pooled donated blood and contains high titres of antibodies to hepatitis B, cytomegalovirus, varicella, tetanus toxin, etc. In addition, preparations of specific high-titre immunoglobulin, derived from the blood of donors with especially high levels of antibodies, such as hepatitis B immunoglobulin (HBIG), zoster immunoglobulin (ZIG, for use after exposure to varicella or zoster), rabies immunoglobulin (RIG) and tetanus immunoglobulin (TIG), are available for use in people who have recently had an exposure to one of these organisms. Recommendations for the use of immunoglobulins are outlined in the relevant specific disease sections of this Handbook, and in section 1.5.

Another example of passive immunity is the passing of protective antibodies from mothers to their infants, both by placental transfer and via breast milk. Maternal antibodies play an important role in early protection against a range of diseases and in attenuating (weakening) infections so that infants can generate their own active immunity without serious illness. A baby born prematurely has a lower concentration of antibodies, and therefore a shorter duration of protection than a full-term infant, and if born before 28 weeks’ gestation will have few or no maternal antibodies.

1.1.4 How vaccines workTop

Vaccines are live microbes that have been attenuated (weakened), whole microbes that have been killed so that they cannot replicate or cause disease, or fragments of the disease-causing microbe.

Administration of a vaccine elicits an immune response that begins with the innate, non-specific cells of the immune system recognising the vaccine antigens. The cells of the innate immune system then stimulate the cells of the adaptive immune system (T and B lymphocytes). Immune memory can last for many years, often for life. Protective levels of antibodies may wane, and a booster dose of vaccine can stimulate the memory cells into developing more antibodies.

Vaccination with killed microbes or with fragments of the microbe commonly requires three or more successive doses over a period of some months to generate effective immune responses. In contrast, a single vaccination with a highly immunogenic vaccine, particularly a live attenuated vaccine, is usually sufficient to generate long-term immune memory. If a further dose (a booster) is given some months or years later, a greater and longer-lasting secondary response can be stimulated, reinforcing and extending the immunological memory for that microbe.