Vaccination in Practice and Public Health

A vaccine is only as useful as the programme that delivers it. Beyond the immunology of the individual response, vaccination is a population intervention whose benefits and failures are properties of whole communities, schedules and surveillance systems, not only of the vaccine itself. A highly effective vaccine achieves little with poor coverage, while even a modest one can control a disease when enough people receive it. The platforms themselves are covered in the Vaccine Types and Platforms article; what follows is how vaccination behaves once it meets a population, ending with the South African programme.

Herd immunity

When a large enough fraction of a population is immune, a virus can no longer find new hosts fast enough to sustain transmission, and even the unvaccinated are protected. This indirect protection, herd (or community) immunity, is what allows vaccination to shield those who cannot be vaccinated themselves: young infants, pregnant women and the immunocompromised.

The threshold depends on how transmissible the virus is, measured by the basic reproduction number (R0), the average number of new infections one case produces in a fully susceptible population. Transmission contracts once each case infects fewer than one further person, so the proportion that must be immune is approximately 1 minus 1/R0. A virus with an R0 of 4 needs about 75% immune; measles, with an R0 of roughly 12 to 18, needs about 95%, which is why measles is the first disease to return when coverage slips.

Herd immunity also reshapes epidemiology. As circulation falls, the average age at infection rises, because susceptible people accumulate. This age-shift matters most for rubella, where infection is trivial in childhood but devastating to a fetus, so a partial programme that merely delayed infection into the childbearing years could do net harm. The response is to aim for high coverage in both sexes.

Vaccination also exerts selection pressure on the virus. Sustained immune pressure can favour escape: under widespread vaccine and immunoglobulin use, hepatitis B surface-antigen escape mutants have been described, and the same principle drives surveillance for vaccine escape in other viruses. The effect is generally modest where the protective surface antigen is conserved and structurally constrained, and greatest where it can vary freely.

Vaccine failure

A vaccinated person who is nonetheless infected has experienced vaccine failure, and the distinction between its two forms is clinically important.

Primary vaccine failure is the failure to respond to the vaccine at all: the person never seroconverts. Its causes include maternal antibody neutralising a live vaccine in young infants, vaccination at too young an age, host immunocompromise (advanced HIV, congenital immunodeficiency, immunosuppressive therapy), and, for heat-labile live vaccines, a broken cold chain. About 10% to 15% of infants fail to seroconvert to a first measles dose given at 9 months, one reason a second dose is scheduled.

Secondary vaccine failure is waning immunity in someone who did initially respond. Vaccine-induced antibody can fall below the protective threshold over years, particularly where natural boosting from circulating virus has disappeared. Resurgent mumps in highly vaccinated young adults is the standard example, and the rationale for booster doses.

Vaccine safety and adverse events

Most vaccine reactions are mild and expected: local pain and swelling, fever and transient malaise, collectively reactogenicity, which reflects the immune activation the vaccine is meant to produce. Genuinely serious adverse events are rare and are the proper focus of safety monitoring.

A few historical vaccines caused enhanced disease, in which vaccination worsened rather than prevented later infection. The formalin-inactivated respiratory syncytial virus (RSV) vaccine of the 1960s is the defining case: it raised non-neutralising antibody and a skewed T cell response, so vaccinated children suffered more severe disease on natural infection, with deaths. An inactivated measles vaccine caused an analogous atypical measles as antibody waned. These episodes established that the quality of a vaccine response must be characterised, not just its size, and they explain the caution applied to novel inactivated and subunit designs.

Because serious events are rare, they are detected by post-marketing surveillance rather than by pre-licensure trials. Passive systems collect suspected adverse events following immunisation (AEFI) and dedicated databases test safety signals against expected background rates. Public confidence depends on this transparency: the claimed link between the measles, mumps and rubella (MMR) vaccine and autism, based on fraudulent and retracted work, has been refuted by many large studies showing no association, yet the episode caused lasting falls in coverage and resurgent measles.

Immunity itself can be measured to guide practice. Serological assays document seroconversion after vaccination (an anti-HBs titre above 10 milli-international units per millilitre confirms hepatitis B protection) or susceptibility before it. Such tests have limits, because antibody titre does not capture cellular immunity and a validated correlate of protection exists for only some vaccines.

Developing and licensing a vaccine

A vaccine moves from concept to use through staged human trials after preclinical work. Phase I, in a few dozen volunteers, tests safety and dose; phase II, in hundreds, assesses the immune response and refines the schedule; and phase III, in thousands to tens of thousands, tests efficacy and detects less common adverse events. Licensure is followed by phase IV post-marketing surveillance. Where a correlate of protection is established, a vaccine can be licensed on the immune marker instead of a full disease-endpoint trial, as for influenza.

Speed has become possible without skipping these steps. The COVID-19 vaccines compressed development into under a year by running the phases in overlapping rather than strictly sequential order, manufacturing at financial risk before results were known, and building on platform technology developed in advance. The same logic, a ready platform onto which a new antigen is dropped, underlies pandemic-preparedness programmes.

Schedules and special populations

Immunisation schedules are engineered, not arbitrary. A primary course is timed to the earliest age at which the infant will respond once maternal antibody has waned, with later doses to catch primary failures and sustain immunity. Three rules follow: an interrupted course is resumed, never restarted; two live parenteral vaccines are given on the same day or at least four weeks apart; and combination products are used only as licensed.

Particular groups need particular handling:

• Infants respond poorly to some antigens because of immune immaturity and maternal antibody, addressed by multi-dose courses and increasingly by maternal immunisation, vaccinating in pregnancy so transferred antibody protects the newborn (used for influenza, pertussis and now RSV).
• The elderly mount weaker responses through immunosenescence, met with higher-dose or adjuvanted formulations.
• Pregnant women are given inactivated vaccines such as influenza, while live vaccines are avoided.
• Immunocompromised people cannot receive live vaccines and may respond weakly to non-live ones, so timing around immunosuppression and protection of household contacts (cocooning) both matter.
• Healthcare workers are a defined priority group, for whom hepatitis B, influenza, measles and varicella immunity protects both themselves and their patients.

Surveillance, elimination and eradication

Two end-states are distinguished. Elimination is the reduction of a disease to zero cases in a defined area, which must be sustained by ongoing vaccination because the virus persists elsewhere. Eradication is permanent worldwide reduction to zero, after which vaccination can stop; it is achievable only for a virus with no animal reservoir, no long-term carrier state and an effective vaccine. Smallpox remains the only eradicated human disease (declared 1980); the animal morbillivirus rinderpest followed in 2011. Polio and measles are the current eradication targets.

Polio shows both the promise and the difficulty. Wild poliovirus is nearly gone, but the live oral vaccine can rarely revert and seed circulating vaccine-derived poliovirus (cVDPV) outbreaks where coverage is low, which is why programmes are moving to newer oral vaccine strains and to inactivated vaccine.

Surveillance underpins all of this. Global networks track both the viruses and the diseases: the Global Influenza Surveillance and Response System selects each season’s influenza strains, while acute flaccid paralysis and measles surveillance detect importations and outbreaks. Active and passive immunisation combine in outbreak control: ring vaccination, immunising the contacts around each case, helped eradicate smallpox, and immunoglobulin gives immediate protection to exposed susceptible people while a vaccine takes effect.

South African context

South Africa delivers childhood vaccination through the Expanded Programme on Immunisation (EPI-SA), launched in 1974 and revised on the advice of the National Advisory Group on Immunisation (NAGI), the country’s national immunisation technical advisory group. Adverse events following immunisation are reported to the regulator, the South African Health Products Regulatory Authority (SAHPRA), and assessed for causality by the National Immunisation Safety Committee. The current routine schedule is below, with the viral vaccines identified.

Age	EPI vaccines	Viral components
Birth	Bivalent oral polio (bOPV); BCG	bOPV; hepatitis B only if mother HBsAg-positive
6 weeks	bOPV; rotavirus; hexavalent (DTaP-IPV-Hib-HBV); PCV	rotavirus; polio and hepatitis B (in hexavalent)
10 weeks	Hexavalent	polio; hepatitis B
14 weeks	Rotavirus; hexavalent; PCV	rotavirus; polio; hepatitis B
6 months	Measles-rubella (MR), dose 1	measles; rubella
9 months	PCV	none
12 months	Measles-rubella (MR), dose 2	measles; rubella
18 months	Hexavalent booster	polio; hepatitis B
6 years	Tdap	none
~9 years (girls)	HPV (single dose, schools)	HPV
12 years	Tdap	none

Several features are distinctive. The hepatitis B birth dose is targeted, given only to infants of HBsAg-positive mothers, with routine hepatitis B otherwise delivered inside the hexavalent vaccine; a universal birth dose, which the World Health Organization recommends, is not yet policy and is a recognised gap. The first measles-rubella dose is given at 6 months, earlier than the 9-month licensed minimum and so off-label, a deliberate measles-control measure in a high-transmission, high-HIV-prevalence setting. The rotavirus course must be completed early, with no dose given after 24 weeks of age. HPV vaccine is offered to girls only, as a single dose, through public schools, with a catch-up for those previously missed.

HIV shapes vaccination. Children with asymptomatic HIV receive all EPI vaccines, but the live vaccines (BCG, oral polio, rotavirus and measles) are withheld in symptomatic HIV or AIDS because of the risk of disseminated vaccine-strain infection, and an additional early measles dose is given to HIV-infected infants. There are no interactions between antiretroviral therapy and the EPI vaccines.

Gaps remain. Coverage sits below target, with first-dose measles coverage around 82% against a 95% goal, and pockets of zero-dose children, who receive no vaccines at all, reaching about 40% in the worst-affected districts. Varicella, hepatitis A, mumps-containing (MMR) and seasonal influenza vaccines are available only in the private sector, and HPV vaccination does not extend to boys. Influenza and COVID-19 vaccines sit outside the routine EPI schedule.

References and recommended reading

• Crowe JE Jr. Immunization Against Viral Diseases. In: Fields Virology, 7th edition (Fundamentals), Chapter 15. Wolters Kluwer; 2023. Current reference for correlates of protection, special populations and eradication.
• Burrell CJ, Howard CR, Murphy FA. Vaccines and Vaccination. In: Fenner and White’s Medical Virology, 5th edition, Chapter 11. Academic Press / Elsevier; 2017. Foundational account of herd immunity, vaccine failure and programme principles.
• Ledgerwood JE, Graham BS. Immunization Against Viral Diseases. In: Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition, Chapter 17. ASM Press; 2016. Foundational reference for the herd-immunity threshold and vaccine failure.
• National Department of Health, South Africa. Expanded Programme on Immunisation (EPI-SA): routine childhood immunisation schedule and programme overview, 2024 revision. The authoritative source for the South African schedule, governance and coverage.