Viral Disease: Immunity, Vaccines and Prevention

1Overview

In 2009 a new influenza virus appeared and spread around the world within months. A few years earlier, a single unvaccinated traveller returning from abroad was enough to start a measles outbreak in a country that had nearly eliminated the disease. Viral disease is not only a medical subject: it shows biology at work at the levels of molecules, cells, organisms, populations and ecosystems. This lesson follows a virus from its first contact with a body, through the immune response, to the strategies that stop it from spreading through a whole population.

2How the body defends itself: innate and adaptive immunity

The immune system has two broad layers. The innate response is fast and general. The adaptive response is slower, highly specific and remembers what it met.

Innate defences

• Barriers: intact skin, mucus, tears, cilia and stomach acid block or remove pathogens.
• Phagocytes such as macrophages and neutrophils engulf pathogens and debris.
• Interferons are signals released by virus-infected cells. Neighbouring cells that receive them break down RNA and reduce protein synthesis, which limits viral replication.
• Inflammation makes blood vessels leakier so that immune cells and fluid reach the site of infection, producing redness, swelling, heat and pain.
• Fever is caused by cytokines raising body temperature. See the article on why fevers happen.

Adaptive immunity

Adaptive immunity develops over days to weeks and is directed at specific antigens, foreign molecules that immune cells recognize. Its main players are:

• B cells, which bind an intact antigen. With help from helper T cells they multiply and become antibody-secreting plasma cells and memory B cells.
• Antibodies, proteins that match a specific antigen and help to disable pathogens and mark them for phagocytes.
• Helper T cells, which release cytokines and coordinate other immune cells.
• Cytotoxic T cells, which recognize infected cells and kill them. They are especially important against viruses because viruses hide inside cells, where antibodies cannot reach.
• Memory cells, long-lived B and T cells that persist for years or decades and respond rapidly if the same antigen returns.

The primary response to a first exposure is slow and produces a modest amount of antibody. The secondary response after a later exposure begins sooner and produces much more antibody, because memory cells skip the early activation steps. This difference is the entire basis of vaccination. See also the article on how the immune system works.

3Vaccines

A vaccine delivers harmless antigens from a pathogen so that the immune system forms memory cells without the person becoming ill. A vaccine produces a mild primary response; later exposure to the real pathogen triggers the fast secondary response. Memory cells can decline over time, which is why some vaccines need booster doses (tetanus boosters about every ten years are a standard example).

Vaccines undergo extensive safety testing before approval, and research supported by public health bodies concludes that their benefits in preventing illness and death greatly outweigh their risks. A worldwide vaccination campaign eradicated smallpox in the 1970s. After a vaccine against Haemophilus influenzae type b (Hib) was introduced in the mid-1980s, the incidence of Hib disease in the United States dropped by 99%.

4Herd immunity

Herd immunity (also called community immunity) occurs when enough people in a population are immune that a disease has little room to spread. An infected person meets mostly immune people, so the chain of transmission is broken. The protection extends to those who cannot be vaccinated, such as newborns and people with weakened immune systems.

The proportion of the population that must be immune depends on how contagious the disease is: more contagious diseases need higher immunization rates to stop transmission. Measles is highly contagious, so even small gaps in coverage can allow outbreaks. Even where a disease is not eliminated, high coverage makes epidemics less frequent.

5How viral diseases spread, and how to reduce the spread

Preventing a viral disease means breaking the chain of transmission at one or more links.

6Case studies of viral disease

H1N1: new viruses from mixing genes

The influenza genome is made of separate segments. When two flu viruses infect the same cell, their segments can be mixed, a process called reassortment. The 2009 H1N1 virus was first detected in people in the United States in April 2009. Six of its eight genes match viruses that regularly infect pigs in North America, and the other two match viruses previously found only in Eurasian pigs. Some of these genes came from viruses that had spread among humans and birds. Pigs can carry bird, human and swine flu viruses at once, so they can act as a "mixing vessel". Reassortment can cause an abrupt, major change called antigenic shift, so that most people have little or no protection against the new virus.

Avian influenza: crossing from animals to people

Wild aquatic birds are the main natural reservoir for most avian influenza A viruses. Infections also occur in poultry and some mammals. Most human infections follow direct contact with infected birds or other animals, for example handling or processing them, and properly cooked poultry and eggs are not considered a route of transmission. The currently circulating avian viruses have not shown sustained spread between people. A pandemic would need a new influenza A virus that spreads continuously between people and to which the population has little or no immunity, and because wild birds carry the viruses, eliminating them is not possible. Surveillance in animals and people is therefore a key control.

HIV: a retrovirus and the immune system

HIV targets white blood cells and weakens the immune system, making other infections and some cancers more likely. It spreads through blood, semen, vaginal fluids and breast milk, and from mother to child during pregnancy, birth or breastfeeding. It is not spread by kissing, hugging, handshakes or shared food or objects. Prevention includes condoms, testing, safe injection practices, PrEP (antiretroviral medication taken by HIV-negative people to lower risk) and PEP (taken after a possible exposure). Antiretroviral therapy suppresses the virus, lets the immune system recover and allows people to live long, healthy lives. People with an undetectable viral load do not transmit HIV sexually. There is no cure: ART controls HIV but does not eliminate it, which fits with the integration of HIV DNA into the host genome described in the previous lesson. Untreated HIV can progress, often after many years, to AIDS, the most advanced stage.

Ebola: control without a cure for everyone

Ebola disease has an incubation period of 2 to 21 days. Early signs are sudden fever, fatigue, muscle pain, headache and sore throat; later signs include vomiting, diarrhoea and rash. Bleeding is less common than often assumed. People are not infectious before symptoms appear. The virus spreads through contact with blood or body fluids of a sick or deceased person, and burial practices involving direct contact can spread it. Health workers are at risk when infection control precautions are not strictly followed. Outbreak control combines isolation of patients, contact tracing and 21 days of monitoring for contacts, infection prevention in health facilities, safe and dignified burials, community involvement and, for Ebola virus disease, vaccination.

Viral STIs

Hepatitis B, herpes simplex virus, HIV and human papillomavirus (HPV) are viral sexually transmitted infections. Safe, effective vaccines exist for HPV and hepatitis B. Condoms, used correctly and consistently, are among the most effective protections, although they do not fully protect against infections that cause sores outside the genital area, such as genital herpes. Many STIs have no symptoms, so testing is important. Some STIs can pass from mother to child during pregnancy, childbirth and breastfeeding.

7Preventing the next pandemic

The Curricular Competencies invite students to plan how drug companies, health agencies and governments could prevent pandemics. A reasoned plan can be organized by link in the chain:

• At the source: monitor viruses in animals such as birds and pigs, because viruses can cross to people and reassort in animal hosts.
• In populations: maintain high vaccination coverage, offer testing and give clear public information.
• In health systems: isolate cases, trace contacts, follow infection control, and develop vaccines and antiviral drugs that target viral enzymes.
• Across borders: share surveillance data, because travel moves infections quickly between regions.

8Summary

• Innate defences act fast; adaptive immunity is specific and creates memory, giving a stronger secondary response.
• Vaccines present harmless antigens so that memory forms without the disease.
• Herd immunity protects a population, including those who cannot be vaccinated; the coverage needed rises with contagiousness.
• Control measures target links in the chain of transmission.
• H1N1 arose by reassortment; avian flu is a zoonotic risk; HIV is controlled by antiretroviral therapy and prevention; Ebola is controlled by isolation, safe burials and vaccination; vaccines exist for the viral STIs HPV and hepatitis B.

?Quick check

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