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Effectiveness of inactivated influenza vaccines

The efficacy (prevention of illness among vaccinated individuals in controlled trials) and effectiveness (prevention of illness in vaccinated populations) of influenza vaccines is dependent on several factors. Research comparing vaccinated with unvaccinated participants show outcome measures that include laboratory-confirmed infection with influenza virus provide the most robust evidence of vaccine efficacy. 

The age, immune status and health of the recipient are important as well as the match between circulating viral strains and the vaccine strains. The type of vaccine can also influence how effective an influenza vaccine is. The inclusion of an adjuvant in influenza vaccines is one approach to enhance a person’s immune response to the vaccine, (1,2) which could benefit older adults experiencing a natural decline in immune function associated with ageing. (3-6) 

Trivalent influenza vaccines contain two influenza A strains (a H1N1 and a H3N2 strain) and one influenza B strain (from either the Yamagata or Victoria line). Quadrivalent influenza vaccines contain two influenza A strains (a H1N1 and a H3N2) and two influenza B strains (one from each line). Receipt of a quadrivalent influenza vaccine broadens the immune response, which may provide additional protection if influenza B viruses from both lines are circulating, or the predominant circulating influenza B virus is not from the line included in the trivalent vaccine. (7) 

When influenza vaccine strains match circulating influenza viruses, protection against influenza is primarily dependent on circulating antibodies. These peak during the first month after vaccination and decrease over 6 months (influenza A (H1N1) and B viruses) or 5 months (influenza A (H3N2) viruses) after vaccination. (8) 

Influenza vaccines are effective in children. However, less evidence is available for children aged under 2 years. (9,10) In healthy adults, influenza vaccines are effective in reducing cases of influenza particularly when the vaccine and circulating virus strains are well matched. (9,11) Inactivated influenza vaccine effectiveness is around 60% against laboratory-confirmed influenza and just below 20% against influenza-like illness. (12) Vaccine effectiveness may not be as high in older people. (13-17) 

However, older people who have been vaccinated but subsequently get influenza are less likely to have severe disease (18, 19) or complications, (17,19,20,21) including cardiovascular events, (20,22,23) cerebrovascular events, (23) hospitalisation, (14,17,24) increased disability or frailty (25,26) or influenza-related death. (14,24) The table on the following page summarises selected current estimates of inactivated influenza vaccine efficacy and/ or effectiveness against a range of clinical outcomes. 

Pooled New Zealand data from the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) study have shown that non-adjuvanted influenza vaccine effectiveness over 2012–2015 was around 46% (95% confidence interval 35–55%) in preventing influenza-like illness presentations to general practice and 52% (41–62%) preventing influenza-related hospitalisations.(10, 27-29) 

Low influenza activity in 2018 caused imprecision in the assessment of influenza vaccine effectiveness.
Estimated vaccine effectiveness in preventing influenza- like illness presentations to general practice was 38% (95% confidence interval 1–61%) and in preventing influenza-related hospitalisations was 35% (95% confidence interval 12–52%).(30)

Effectiveness can be reduced by a difference between circulating virus strains and vaccine strains. The influenza virus keeps changing and new vaccines are formulated for each northern and southern hemisphere season. There may be some cross protection against a virus type that is not in the vaccine but the amount of protection cannot be guaranteed or easily quantified.

How long after vaccination does it take for antibodies to be produced?

It can take up to 2 weeks for the vaccine to provide the best influenza protection. However, influenza vaccinations can be given when influenza virus activity has been identified as protective antibody levels have been observed to develop rapidly from 4 days after vaccination. (31)

Table: Selected current estimates of inactivated influenza vaccine efficacy and/or effectiveness against a range of clinical outcomes

Type of Outcome
Level of protection
(95% confidence intervals)

Pregnant women

Effectiveness against

  • confirmed influenza
  • acute respiratory illness requiring an
  • - emergency department visit or
  • - hospitalisation

50% (15–71%)32

81% (31–95%)33

65% (3–87%)33

Infants aged under 6 months

whose mothers received an influenza vaccination during pregnancy

Effectiveness against

  • confirmed influenza
  • influenza-related hospitalisation

41% (7–63%)34 to
49% (12–70%)12,32

47% (12–68%)35

Healthy children

  • aged under 2 years

  • aged 6–35 months

  • aged 6 months to 17 years

  • aged 2–15 years

Effectiveness against

  • confirmed influenza

  • confirmed influenza

  • influenza-related death

Efficacy against confirmed influenza

Effectiveness against

  • influenza-related hospitalisation
  • influenza-like illness

Insufficient data9,10
66% (9–88%)36

66% (29–84%)36

65% (47–78%)37

64% (52–72%)10

56% (12–78%)38

28% (21–35%) to 47% (33–58%)10

with a high-risk condition
aged 6 months to 17 years

Effectiveness against influenza-related death

50% (15–71%)37

Healthy adults

aged 18–64 years

Effectiveness against

  • confirmed influenza
  • influenza-related hospitalisation in NZ
  • influenza-like illness
  • influenza-like general practice

59% (53–64%) to 66% (55–75%)12

61% (34–77%)11

16% (5–25%) to 18% (2–31%)12

55% (24–73%)11

Adults with high-risk conditions

  • heart failure
  • diabetes (newly diagnosed, age 65 years or older)

  • chronic obstructive pulmonary disease

Risk of

  • all-cause mortality
  • all-cause mortality
  • influenza-related hospitalisation

Effectiveness against influenza-related hospitalisation

17% reduced risk39

56% reduced risk40

11% reduced risk40

22% (15–27%) to 43% (35–52%)41

Adults aged 40 years or older

Effectiveness against acute myocardial infarction

29% (9–44%)42

Adults aged 65 years or older

Effectiveness against

  • confirmed influenza

  • influenza-like illness

  • pneumonia/influenza related hospitalisation in community-dwelling elderly
  • non-fatal and fatal complications

MF59 adjuvanted vaccines are in bold
49% (33–62%)14
58% (34–73%)16
60% (-1.3–84%)17

39% (35–43%)14
41% (27–53%)16

51% (39–61)17

28% (26–30%)14

Some studies have suggested residual protection from prior season influenza vaccination influences current season vaccine efficacy and/or antibody waning. (8,43-45) Pooled analyses of these studies are inconclusive and have highlighted an area for further research. (7,43,45) However, a review of 15 influenza seasons in Italy, (46) where around two-thirds of older adults received a MF59 adjuvanted influenza vaccine and one-third a non-adjuvanted vaccine, found that the reduction in risk associated with influenza vaccination was not affected by prior season influenza vaccination. (46)

An increasing body of evidence supports the significant role of prior and current season influenza vaccination in reducing the risk of influenza related hospitalisation with severe illness, (18,47) ischaemic stroke, (48,49) heart failure,(50) and acute coronary syndrome, (51,52) acute myocardial infarction,(53,54)o respiratory disease.(52) A protective effective of cumulative influenza vaccination has also been identified through an improved survival rate in vaccinated adults with heart failure. (55)

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