Live attenuated vaccines (LAV)

Immune response

LAVs stimulate an excellent immune responseImmune responseThe body's defense against foreign objects or organisms, such as bacteria, viruses or transplanted organs or tissue. that is nearly as good as compared to an infection with the wild-type pathogen.

Live microorganismsMicroorganismsTiny organisms (including bacteria and viruses) that can only be seen with a microscope. provide continual antigenic stimulation giving sufficient time for memory cell production.

In the case of viruses or intracellular microorganisms where cell-mediated immunityCell-mediated immunityAn immune response not involving antibodies, in which specific blood cells, leukocytes, and lymphocytes attack and remove antigens. is usually desired, attenuated pathogens are capable of replicating within host cells.

Safety and stability

Since LAVs contain living organisms, there is a degree of unpredictability raising some safety and stability concerns.

  • Attenuated pathogens have the very rare potential to revert to a pathogenic form and cause disease in vaccinees or their contacts. Examples for this are the very rare, serious adverse events of:
    • vaccine-associated paralytic poliomyelitis (VAPP) and
    • disease-causing vaccine-derived poliovirus (VDPV) associated with oral polio vaccine (OPV).
  • Functional immune systems eliminate attenuated pathogens in their immune response. Individuals with compromised immune systems, such as HIV-infected patients may not be able to respond adequately to the attenuated antigens.
  • Sustained infection, for example tuberculosis (BCG) vaccination can result in local lymphadenitis or a disseminated infection.
  • If the vaccine is grown in a contaminated tissue culture it can be contaminated by other viruses (e.g. retro-viruses with measles vaccine).
  • Theoretically, live attenuated virus vaccines given to pregnant women might be capable of crossing the placenta and infecting the foetus. As a result, most live attenuated vaccines are contraindicated or not recommended during pregnancy.85
  • LAVs are contraindicated for patients following cancer treatment and for patients who have finished a cancer treatment for less than 6 months. Other types of vaccines are allowed during cancer treatment.91
  • LAVs can have increased potential for immunization errors:
    • Some LAVs come in lyophilized (powder) form. They must be reconstituted with a specific diluent before administration, which carries the potential for programmatic errors if the wrong diluent or a drug is used.
    • Many LAVs require strict attention to the cold chain for the vaccine to be active and are subject to programme failure when this is not adhered to.

Adverse reactions associated with LAVs

Five vaccines that are recommended by WHO are produced using LAV technology which are displayed in the table below:

  • Tuberculosis (BCG),
  • Oral Polio Vaccine,
  • Measles,
  • Rotavirus,
  • Yellow Fever.

The table lists the rare, more severe adverse reactions of these vaccines. Note the frequency of the adverse reactions to get an idea of how low or high the possibility of an adverse event is. Also read the Comments to understand additional context details on the adverse events.

Five WHO recommended vaccines using LAV technology

  Vaccine Rare, more severe adverse reactions Frequency Comment
Tuberculosis (BCG)28 Fatal dissemination of BCG infectionFatal dissemination of BCG infectionTuberculosis (BCG) vaccine-induced infection that is spread over a large area of the body, a tissue, or an organ, and results in death. very rare at 1.56–4.29 per million doses Almost exclusively occurs in inadvertently immunized persons with severely compromised cellular immunity.
Osteitis and Osteomyelitis very rare In the past BCG osteitis has been reported in connection with certain vaccine batches but now occurs very rarely.
Oral polio vaccine (OPV)29 Vaccine-associated paralytic poliomyelitis
(VAPP) in vaccinees
and their contactsVaccine-associated paralytic poliomyelitis (VAPP)A very rare risk of paralytic polio resulting from oral poliomyelitis vaccine (OPV). Associated with approximately one in every 2.5 million doses of OPV. VAPP is not a risk with IPV.
very rare at
2–4 per million doses
An essential component of the global polio eradicationEradicationThe complete and permanent worldwide reduction to zero new cases of an infectious disease through deliberate efforts; no further control measures are required. campaign despite adverse reactions.
Measles31 Febrile seizuresFebrileRelating to fever; feverish. A febrile seizure is a seizure or convulsion that occurs during a high fever. Common in children under five years of age, rarely resulting in long term injury. uncommon at
3.4–8.7 per 10,000 doses
Adverse reactions, with the exception of allergic anaphylactic reactions, are less likely to occur after receipt of the second dose of measles vaccine.
Transient thrombocytopenia very rare at 2.5–3 per 100,000 dose
AnaphylaxisAnaphylaxisAn acute, multi-system, allergic reaction (IgE mediated) to a substance, such as vaccination, drugs, and food. Symptoms of anaphylaxis may include breathing difficulties, loss of consciousness, and a drop in blood pressure. This condition can be fatal and requires immediate medical attention. very rare at 3.5–10 per million doses Allergic reactions to vaccine components including neomycinNeomycinA broad-spectrum antibiotic that is used in the manufacture of some vaccines. and the stabilizersStabilizersCompounds that are used to help vaccine maintain its effectiveness during storage. Vaccine stability is essential, particularly where the cold chain is unreliable. Factors affecting stability are temperature and pH. gelatine or sorbitolSorbitolAn alcohol used in the manufacture of some vaccines., may follow vaccination.
Rotavirus61 Intussuception 1–2/100,000 infants To date, post-licensure surveillance does not indicate any increased risk of intussusceptionIntussusceptionA potentially life threatening obstruction of the bowel. When the first rotavirus vaccine was licensed in 1999, it was withdrawn from the market following evidence linking it to a small increase in the risk of intussusception. or other serious adverse reaction associated with the use of current rotavirus vaccinesRotavirus vaccineA preparation of live attenuated rotavirus used to immunize against infant rotaviral gastroenteritis..
Yellow fever (YF)62 Hypersensitivity or anaphylactic reactionsHypersensitivityAn excessive or abnormal sensitivity in a body tissue to an antigen or foreign substance. 0.8 per 100,000 doses SensitivitySensitivityIn the context of public health surveillance, the proportion of all incident cases of a health condition detected by a surveillance system. to egg, which is commonly used to stabilize the vaccine, may explain at least some of these cases.
Vaccine-associated neurotropic diseaseVaccine-associated neurotropic diseaseA very rare disease of the nervous system that follows vaccination against yellow fever. (encephalitisEncephalitisRefers to an encephalopathy caused by an inflammatory response in the brain. This is usually manifested with systemic constitutional symptoms, particularly fever and pleocytosis of the cerebrospinal fluid. However, the terms encephalopathy and encephalitis have been used imprecisely and even interchangeably in the literature.) 0.25–0.8 per 100,000 doses Infants seem more susceptible to vaccine-associated neurotropic disease than the YF-vaccinated population at large.
Vaccine-associated viscerotropic diseaseVaccine-associated viscerotropic diseaseA disease that presents with fever, liver damage and blood disorders that very rarely results from vaccination against yellow fever. 0.25 to 0.4 per 100,000 The elderly seem more susceptible to reaction (very rare at 4–5 per 10,000 doses) than the YF-vaccinated population at large.


Which of the following statements is correct? (Several answers possible)

A. Febrile seizures are an uncommon reaction to vaccination with measles.
B. Compared to giving the first dose of measles vaccine, allergic reactions are less likely to occur during the second dose of measles vaccine.
C. Live vaccines include BCG, Measles, Rotavirus, Pertussis vaccine and Yellow fever vaccine.
D. Vaccine associated paralytic poliomyelitis occurs very rarely among vaccines (2 – 4 cases per 1 000 000 vaccinated persons).


Answers A and D are correct.

Answer B: Allergic anaphylactic reactions are more likely to occur after receipt of the second dose of measles vaccine.

Answer C: Pertussis (wP) is an inactivated vaccine. Live vaccines include:

  • Tuberculosis (BCG)
  • Oral Polio Vaccine,
  • Measle,
  • Rotavirus,
  • Yellow Fever.