Contents

10 Influenza

10.4 Vaccines

Annual influenza vaccination for those at risk of complications of infection is the single most important measure for preventing influenza infection and mortality. The National Influenza Specialist Group (NISG) is responsible for New Zealand’s annual Influenza Communication Campaign (www.influenza.org.nz). This campaign includes an influenza kit for health care professionals and a national education and communication programme.

Funded vaccines

The trivalent inactivated split virion influenza vaccines funded in New Zealand are:
  • Influvac (Mylan), containing 15 µg of each of the three recommended influenza strains; other components and excipients include potassium chloride, potassium phosphate monobasic, sodium phosphate-dibasic dihydrate, sodium chloride, calcium chloride and magnesium chloride
  • ​Fluarix (GSK), containing 15 µg of each of the three recommended influenza strains; other components and excipients include saccharose, d-alpha-tocopheryl acid succinate and traces of formaldehyde and gentamicin sulphate.

Other vaccines

Other influenza vaccine brands registered and available in New Zealand are:

10.4.1 Vaccine preparations

Influenza vaccine preparations vary by their type, the number of influenza strains contained in the vaccine and their delivery systems. The adjuvanted and live attenuated vaccines have improved efficacy, particularly for some groups, but the safety data needs to be further assessed.

Vaccine types

Inactivated influenza vaccines (split virion or subunit vaccines)

The trivalent inactivated vaccines (TIV) available in New Zealand are inactivated split virion vaccines prepared from virus grown in the allantoic cavity of embryonated eggs. The virus is purified, disrupted and inactivated with beta-propiolactone or formaldehyde.

One inactivated quadrivalent influenza vaccine (FluQuadri, Sanofi-aventis NZ Ltd) is now registered and available in New Zealand. Inactivated quadrivalent vaccines were used in the US10 and in some European countries for the 2013/14 influenza season and in Australia in 2014 to improve strain matching.

Live attenuated influenza virus vaccines

Live attenuated influenza virus (LAIV) vaccines (trivalent and quadrivalent) are a new technology licensed for use in North America for healthy non-pregnant individuals aged 2–49 years and in Europe for children aged 2–18 years. At the time of writing, LAIV vaccines were not registered in New Zealand.

Adjuvanted vaccines

Adjuvants enhance the immune response to an antigen. There are three new adjuvants licensed (internationally) for use in influenza vaccines: two oil-in-water emulsions, and a third that uses immunopotentiating reconstituted influenza virosomes.11

Vaccines with these adjuvants have modestly improved immune responses, but may also cause more local and systemic reactions than unadjuvanted vaccines.11 At the time of writing, influenza vaccines containing these adjuvants were not registered and/or available in New Zealand.

Number of strains

Trivalent vaccines

The majority of influenza vaccines are trivalent, containing three influenza strains. The strains vary each year depending on the prevailing virus subtypes. The current trivalent vaccines used in New Zealand contain two influenza A strains (eg, H1N1, H3N2) and one prevailing B strain. The WHO recommends the strains for inclusion in September/ October of each year, following the southern hemisphere strain selection meeting. Strain selection may differ from that of the northern hemisphere.

Since 2010 the H1N1 component of the trivalent vaccine has been the 2009 pandemic strain.

Quadrivalent vaccines

Quadrivalent vaccines contain four influenza strains (currently two A strains and two B strains). Since four influenza strains co-circulate each year in New Zealand (see section 10.3.1), a quadrivalent vaccine would likely be beneficial to improve the vaccine strain match with circulating strains. One quadrivalent vaccine is registered and available in New Zealand.

Monovalent pandemic H1N1 vaccine

A monovalent vaccine directed against the A(H1N1)pdm09 strain was approved for use in New Zealand in January 2010. This vaccine was prepared in mammalian cells rather than eggs. The vaccine was offered to specific target groups (including front-line health care workers) as part of the national pandemic response. Its use became redundant once the 2010 trivalent seasonal vaccine (containing the pandemic strain) became available.

Vaccine delivery systems

Intramuscular

With the exception of the intradermal vaccine described below, the seasonal influenza vaccines available in New Zealand are all delivered by intramuscular injection.

Intradermal

Intradermal vaccines are generally recognised as offering similar immune responses in healthy subjects12 and possibly more efficient immune responses,13 particularly in the older adult population.14

The intradermal influenza vaccine (Intanza, Sanofi-aventis NZ Ltd) registered in New Zealand has a prefilled microinjection device that delivers vaccine into the dermis of the skin. The needle is 90 percent shorter than needles used for intramuscular administration. Compared to intramuscular vaccines, the intradermal vaccine has a similar immune response, with a slightly higher rate of injection site reactions.11, 15 Note that the intradermal influenza vaccine was available in 2014 but was discontinued at the end of the 2014 influenza season.

Intranasal mists

Live attenuated influenza vaccines (LAIV), delivered by intranasal spray, induce stronger immune responses than TIVs by mimicking natural influenza infection and evoking both mucosal and systemic immunity, and including broader cellular immune responses.16

10.4.2 Efficacy and effectivenessTop

The efficacy (prevention of illness among vaccinated individuals in controlled trials) and effectiveness (prevention of illness in vaccinated populations) of influenza vaccine depends on several factors. The age and immune competence of the vaccine recipient are important, as well as the match between the virus strains in the vaccine and those in circulation.

The current data for vaccine efficacy and effectiveness of TIV vaccines is summarised in Table 10.1.

Infants and children

The evidence for vaccine efficacy and effectiveness in infants and children is varied. Maternal influenza vaccination is significantly associated with reduced risk of influenza virus infection and hospitalisation for an influenza-like illness in infants up to 6 months of age, and increased influenza antibody titres are seen in infants through to age 2 to 3 months.17 There is evidence to support moderate effectiveness of TIV in children aged 3 years and older.

Healthy adults

Generally, randomised placebo-controlled trials of TIV in healthy adults support good protection against a variety of outcomes, particularly laboratory-confirmed influenza.

Adults aged over 65 years

Although less effective at preventing clinical illness in older people,18 influenza vaccination does reduce hospitalisation and deaths. A 1995 meta-analysis of 20 cohort studies in older people estimated that influenza vaccine prevented 56 percent of upper respiratory illnesses, 53 percent of pneumonias, 50 percent of all hospitalisations and 68 percent of deaths.19

There is wide variability in the estimates of effectiveness of annual influenza vaccination against influenza-like illness in nursing home residents (0–80 percent).11 Vaccination has been demonstrated to prevent hospitalisation and death in these groups,19–22 but a 2010 Cochrane review concluded that there was insufficient evidence to support influenza vaccine effectiveness in the elderly.23 However, researchers have more recently re-examined this review and its methodology and argue that there is substantial evidence for the ability of influenza vaccine to reduce the risk of influenza infection and influenza-related disease and death in the elderly.24

Pregnant women

Pregnant women are at increased risk of hospitalisation from influenza-related cardiorespiratory disorders during the second and third trimesters, and this was especially apparent in the 2009 pandemic.25 Influenza vaccination is expected to have the same efficacy in healthy pregnant women as in other healthy adults.

Table 10.1: Current estimates of TIV influenza vaccine efficacy and effectiveness

Population Type of outcome Level of protection (95% confidence intervals)
Infants aged under 6 months whose mothers received influenza vaccine Efficacy against laboratory-confirmed influenza 41–48%17, 26
Healthy children aged under 2 years Efficacy against laboratory-confirmed influenza Insufficient data27, 28
Effectiveness against laboratory-confirmed influenza 66% (9–88)29
Healthy children aged 6–35 months Effectiveness against laboratory-confirmed influenza 66% (29–84)29
Healthy children aged under 16 years TIV vaccine efficacy in prevention of laboratory-confirmed influenza in randomised controlled trials 59% (41–71)27
Healthy adults aged 18–65 years Effectiveness against influenza-like illness* 30% (17–41)30
Efficacy against influenza symptoms* 73% (54–84)30
Efficacy against laboratory-confirmed influenza 59% (51–67)28
Those aged 65 years and older Effectiveness in preventing influenza, influenza-like-illness, hospitalisations, complications and mortality Inconclusive due to poor quality of studies23
Those aged 65 years and older Effectiveness against non-fatal and fatal complications 28% (26–30)24
Effectiveness against influenza-like illness 39% (35–43)24
Effectiveness against laboratory-confirmed influenza 49% (33–62)24

* From age 16 years.

Adults with co-morbid conditions

Influenza vaccination has been associated with reductions in hospitalisations and deaths among adults with risk factors for influenza complications. Among Danish adults aged under 65 years with underlying medical conditions, vaccination reduced all-cause deaths by 78 percent and hospitalisations attributable to respiratory infections or cardiopulmonary diseases by 87 percent.31 Benefits from influenza vaccination have been observed for both diabetes32 and chronic obstructive pulmonary disease.33 An Australian study of adults aged 40 years and older showed that unvaccinated adults are almost twice as likely as vaccinated adults to have an acute myocardial infarct.34

Herd immunity

There is some evidence to suggest that herd immunity can be achieved, particularly by vaccinating children, if immunisation coverage is very high (greater than 80 percent).35–37 Some studies suggest that herd immunity may also be achieved in nursing homes if immunisation coverage of residents is greater than 80 percent.38 Vaccinating health care workers is likely to be an effective strategy, particularly for nursing homes.39

Duration of immunity

Because influenza strains continually shift, duration of immunity provided by influenza vaccines is difficult to study. However, when the strains stay the same for consecutive years, vaccination in a previous year appears to confer immunity into the next year for healthy adults.11, 40

Protection due to live attenuated influenza vaccines has been demonstrated to persist beyond a year.41, 42

10.4.3 Transport, storage and handlingTop

Transport according to the National Guidelines for Vaccine Storage and Distribution.43 Store at +2oC to +8oC. Do not freeze. Influvac should be stored in the dark.

10.4.4 Dosage and administrationTop

The funded trivalent seasonal influenza vaccine should be administered by intramuscular or subcutaneous injection (see section 2.3). The contents of the syringe must be shaken thoroughly before use. For administration instructions for the intradermal vaccine, see the manufacturer’s data sheet.

Individuals aged 9 years and older

Individuals aged 9 years and older receive a single 0.5 mL intramuscular dose of vaccine.

Children aged under 9 years

Children aged under 9 years who have not previously received influenza vaccine require two doses of vaccine four weeks apart to produce a satisfactory immune response. Children aged 6–35 months are given a 0.25 mL dose (see Table 10.2 and the manufacturer’s data sheet for the dose in children).

Table 10.2: Recommended influenza vaccine doses in children

Age Dose Number of doses
6–35 months 0.25 mL 1 or 2*
3–8 years 0.5 mL 1 or 2*
* Two doses separated by at least four weeks if the vaccine is being used for the first time.
The recommended dosages for young children at different ages may vary between vaccine manufacturers, so check the manufacturer’s data sheet before administering.

There is limited data on which to base the recommendations, but the aim is to reduce reactions, particularly febrile reactions (which are increased in young children), while maintaining an adequate immune response.

Immunosuppressed or immune-deficient individuals

Regardless of their age, previously unvaccinated immunosuppressed or immune-deficient individuals are recommended to receive two doses of influenza vaccine, four weeks apart. One dose is then given in each subsequent year. (See section 4.3).

When to vaccinate

The optimal time to vaccinate people in high-risk groups is usually during March and April. This is in advance of the usual May to September period of influenza activity. The vaccine can be given even when influenza virus activity has been identified, because protective antibody levels develop from four days to two weeks after immunisation.44 The vaccine should be administered annually to maintain immunity and to provide protection against new strains.

Co-administration with other vaccines

Influenza vaccine can be administered with other vaccines, such as pneumococcal polysaccharide vaccine and the scheduled childhood vaccines. Individuals recommended to receive both influenza vaccine and 13-valent pneumococcal conjugate vaccine (PCV13) have an increased risk of fever following concurrent administration of these vaccines.45, 46 Separation of the vaccines by two days can be offered, but is not essential. (See also section 15.6.2).