Infants and Elderly: is your vaccine approved for these ... | Influenza vaccines in infants and elderly, 25 March 2014 Infants and Elderly: is your vaccine approved for these groups?

Influenza vaccines in infants and elderly, 25 March 20141 |

Infants and Elderly: is your vaccine approved for

these groups?

25 March 2014

Infants and Elderly: is your vaccine approved for

these groups?

25 March 2014


Available Influenza vaccines - USA, 2013–14 influenza seasonTIV Standard dose

(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)

Available Influenza vaccines - USA, 2013–14 influenza seasonTIV Standard dose

(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)

Trade name Manufacturer Presentation Mercury content (µg Hg/0.5 mL)

Age indications Route

Afluria bioCSL

0.5 mL single-dose prefilled syringe

0 ≥9 yrs

IM5.0 mL MDV 24.5 ≥9 yrs

Fluarix GSK 0.5 mL single-dose prefilled syringe

0 ≥3 yrs IM

Flucelvax Novartis 0.5 mL single-dose prefilled syringe

0 ≥18 yrs IM

FluLaval ID Biomedical Corporation of Quebec

5.0 mL MDV ≥25 ≥3 yrs IM

Fluvirin Novartis 0.5 mL single-dose prefilled syringe

≤1≥4 yrs

IM5.0 mL MDV 25.0

Fluzone Sanofi Pasteur


0 6-35 mo IM


0 ≥36 mo IM

0.5 mL single-dose prefilled vial

0 ≥36 mo IM

5.0 mL MDV 25.0 ≥6 mo IM

Fluzoneintradermal

Sanofi Pasteur 0.1 mL prefilled microinjection

system

0 18-64 yrs ID


Available Influenza vaccines - USA, 2013–14 influenza season(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)

Available Influenza vaccines - USA, 2013–14 influenza season(http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)

Vaccine Trade name Manufacturer Presentation Mercury content

(µg Hg/0.5 mL)

Age indication

s

Route

Inactivated Influenza Vaccine,

Trivalent, High Dose

Fluzone High-Dose

Sanofi Pasteur0.5 mL single-dose

prefilled syringe

0 ≥65 yrs IM

Inactivated Influenza Vaccine,

Quadrivalent, Standard Dose

Fluarix Quadrivalent

GlaxoSmithKline0.5 mL single-dose

prefilled syringe0.0

≥3 yrs IM

FluLaval Quadrivalent

ID Biomedical Corporation of

Quebec

5.0 mL multi-dose vial

<25.0

≥3 yrs IM

Fluzone Quadrivalent

Sanofi Pasteur


0.0≥3 yrs IM


0.0

≥4 yrs IM0.5 mL single-dose

vial0.0

Recombinant Influenza Vaccine,

Trivalent FluBlok Protein Sciences

0.5 mL single-dose vial

0.0 18-49 yrs IM

Live-attenuated Influenza Vaccine,

Quadrivalent

FluMist Quadrivalent

MedImmune0.2 mL prefilled

intranasal sprayer0.0 (per 0.2 mL) 2-49 yrs IN


Influenza Vaccines in Europe http://www.ecdc.europa.eu/en/healthtopics/seasonal_influenza/vaccines/Pages/influenza_vaccination.aspx

Influenza Vaccines in Europe http://www.ecdc.europa.eu/en/healthtopics/seasonal_influenza/vaccines/Pages/influenza_vaccination.aspx

Manufacturer Name of product Vaccine type Administration route

Age recommended

Abbot healthcare Influvac Inactivated im >6 mthImuvac

AstraZeneca Fluenz Live attenuated intranasal 24 mth to 17 yrs(US trade name Flumist)

Baxter Preflucel Inactivated im >18 yrs

Crucell Viroflu Inactivated/virosomal im >6 mth, increased fever reported in children 6 mth to 5 yrs

Inflexal Inactivated/virosomal im

GlaxoSmithKline Fluarix Inactivated im >6 mthNovartis Agrippal Inactivated im >6 mth

Fluvirin Inactivated im >4 yrs

Optaflu Inactivated im >18 yrs

Fluad

(MF59)

Inactivated im >65 yrs

Omninvest Fluval AB Inactivated im >6 mthPfizer/CSL Australia Afluria Inactivated im

>5 yrsEnzira Inactivated im

Sanofi Pasteur Vaxigrip** Inactivated im >6 mth

Intanza 9µg Inactivated Intradermal >18-59 yrs

Intanza 15µg Inactivated Intradermal >60 yrs


Seasonal Influenza vaccines registered in Australia[Inactivated, IM, 45ug (3 x 15ug) total dose for adults]

Seasonal Influenza vaccines registered in Australia[Inactivated, IM, 45ug (3 x 15ug) total dose for adults]

Currently used � Agrippal (Novartis) (>6mo)

� Fluarix (GSK) (>6mo)

� Fluvax (BioCSL) (>5; 5-9 RA)

� Influvac (Abbott) (>6mo)– Influvac Jr (Abbott)

� Vaxigrip (Sanofi Pasteur) (>6mo)– Vaxigrip Jr (Sanofi Pasteur)

� Intanza (Sanofi Pasteur) (9ug SC) (18-59)

Currently Not supplied� FluAd (Novartis)

(>65y)

� Fluarix Quadrivalent

(GSK) (>3)

� XFLU (GSK)


WHO Age indication (y)

1 Flulaval GSK (IDBiomed) TIV 12-59

2 GC Flu Green Cross TIV 1-59

3 Fluvirin Novartis, UK TIV 1+

4 Vaxigrip Sanofi (France) TIV 1+

5 Fluzone Sanofi (US) TIV 1+

Canada

1 Influvac Abbott TIV subunit 18+

2 Fluviral GSK TIV split 1+

3 Agriflu Novartis TIV subunit 1+

4 Fluad Novartis TIV subunit + Adj. >65

5 Vaxigrip Sanofi TIV split 1+

6 Fluzone Sanofi TIV split 1+

7 Intanza Sanofi TIV-split ID 18+

8 FluMist Medimmune LAIV 2-59


China – TIV split or subunitChina – TIV split or subunit

Age indication

1 Seasonal influenza Beijing Tiantan Biological Products Co., Ltd >4

2 Seasonal influenza Sinovac Biotech Co., Ltd. 1+

3 Seasonal influenza Changchu Institute of Biological Products 1+

4 Seasonal influenza Changchun Changsheng Life Science Co. , Ltd. 1+

5 Seasonal influenza Shanghai Institute of Biological Products 1+

6 Seasonal influenza Hualan Biological Engineering Inc. 1+

7 Seasonal influenza Dalian Hissen Bio-pharm Co., Ltd. 1+

8 Seasonal influenza Dalian Aleph Biomedical Co., Ltd. >4

9 Seasonal influenza Jiangsu Simcere Vaxtec Bio-Pharmac. Co.,Ltd. 1+

10 Seasonal influenza Tasly Jenner Biotech Co., Ltd. Tianjin (sub unit) 1+

11 Seasonal influenza Lanzhou Institute of Biological Products 1+

12 Seasonal influenza Zhejiang Tianyuan Bio-Pharma Co.,Ltd 1+

13 Seasonal influenza Shenzhen Sanofi P. Biol. Products Co., Ltd. 1+


ThailandThailand

Age indication

1 Agrippal S Novartis Germ. TIV 1+

2 Fluzone Sanofi US TIV >3

3 Fluarix GSK, Germ. TIV 1+

4 Vaxigrip Sanofi Fr. TIV-split 1+

5 Fluad Novartis Germ.

TIV subunit +

Adj.1+

6 Fluarix NH GSK, Germ. TIV 1+

7 Influenza vaccine

Sanofi F-GPO-

MBP TIV1+

8 Inflexal V Crucell Switz. Viros adj 1+

9

Split Influenza

Vaccine SIBP, China TIV1+

10 Begrivac Novartis Germ. TIV-split 1+

11 Influvac Abbott NL TIV 1+

12 Intanza 9 ug Sanofi TIV-split ID >18


MexicoMexico

Age indication

1 Fluzone Sanofi US 1+ TIV

2 Vaxigrip Sanofi F 1+ TIV

3 Fluarix GSK B 1+ TIV

4 Agrippal S1 Novartis, Siena 1+ TIV-subunit

5 Influvac Abbott, NL 1+ TIV

6 Fluad Novartis, Siena >4 TIV subunit + Adj.

7 Fluvirene Novartis, UK >4 TIV

8 IDFlu Sanofi F >4 TIV-split ID

9 Ollinflu Birmex (SF) 1+ TIV

10 Fluvaxsin-SV Lab. Imp (Anflu-Sinovac)1+ split


Brazil Age indication

1 Sanofi >2

2 GSK >2

3 Butantan >2

4 Novartis ? ??

Kazakhstan

1 Agrippal S1 Novartis, I >1 TIV-subunit

2 Influvac Abbott, NL >1 TIV

3 Fluarix GSK, G >1 TIV-split

4 Vaxigrip Sanofi, F >1 TIV-split

5 Grippol Petrovax, R >1 TIV-subunit-pol

Romania

1 Fluarix GSK, B >3 TIV

2 Influvac Abbott. NL >1 TIV

3 Intanza /IDFlu Sanofi, F >18 TIV-split ID

4 Optaflu Novartis >18 TIV-cell based

5 Vaxigrip Sanofi, F >1 TIV


Iran

1 Agrippal Novartis >1

2 Fluad Medimmune >1

3 Fluarix GSK >1

4 Inflexal Crucell Switz. >1

5 Vaxigrip Sanofi >1

Indonesia


2 Fluarix GSK >1

3 Agrippal Novartis >1

4 Flubio Bio Farma >18

Serbia

1 Fluad Novartis >65

2 Fluarix GSK >7

3 Fluimum ? >3

4 Intanza Sanofi >59



Differing age indications between countries

Differing age indications between countries

* UK approval

Vaccine EU USA Canada Australia Mexico Serbia Thailand

Fluarix

(GSK)

> 6 months* > 3 years N/A > 6 months > 6 months > 7 years > 6 months

Influvac

(Abbott)

> 6 months* N/A > 18 years > 6 months > 4 years N/A > 6 months

Fluvax

/Afluria/

Enzira

(Bio-CSL)

> 5 Years > 5 Years** N/A > 5 Years** N/A N/A N/A

** 5-9 years use on careful consideration of risks vs benefits


Fluarix (GSK) in the UK> 6 months

Fluarix (GSK) in the UK> 6 months


Fluarix (GSK) in the US> 3 years

Fluarix (GSK) in the US> 3 years


Influvac (Abbott) in UK> 6 months

Influvac (Abbott) in UK> 6 months


Influvac (Abbott) in Canada> 18 years

Influvac (Abbott) in Canada> 18 years


Fluvax / Afluria (Bio CSL) > 5 years

Fluvax / Afluria (Bio CSL) > 5 years


In some studies, split vaccine can be poorly immunogenic in infants

In some studies, split vaccine can be poorly immunogenic in infants

Vesikari et al 2009

% HI>40% HI>40

primeprime boostboostAdjuvant noneAdjuvant none Adjuvant noneAdjuvant none


And in some studies efficacy can also be low…

And in some studies efficacy can also be low…

Vesikari 2011 NEJM

Age Relative efficacy (95% CI)TIV

6-72 Mo 43 (15-61)

36-72 45 (6-68)

6-36 40 (-6-66)

6-24 11 (-89-58)


Vaccine efficacy in the elderlyVaccine efficacy in the elderly

� "young elderly vs old elderly "

� TIV vs adjuvanted TIV in: 65-75, 75-85, >85yr

Van Buynder et al. 2013 Vaccine 31, 6122

� Not all elderly are the same…

Population VE% (univariate)

TIV TIV + adjuvant

All -12 35

Not in long-term care 42 73


Alternative vaccines for the elderlyAlternative vaccines for the elderly

� Adjuvant

� Intradermal delivery

� High dose antigen

– (60 ug vs 15)

0

10

2

4

6

8

ID IMGMTR

HAI GMT

H1N1 H3N2 B

High dose

60 ug

116 609 69

Normal

dose 15 ug

67 333 52


ConclusionsConclusions

� SAGE recommendations include infants and elderly as

priority groups.

– Age indications vary between countries

� Developing vaccines for use in these populations should

include data generation on safety and efficacy

– These populations are variable and clinical trial design and

product development should take this into account

� For these populations there are opportunities to make

targetted improved vaccines

– E.g. SC vaccines, high dose, adjuvanted vaccines, LAIVs,


Considerations for QIVsConsiderations for QIVs

Clinical

Is there interference between the Bs for Ab. response?

Potential extra ADRs because of extra 33 percent of

material

LAIV or recombinant QIVs may be best for safety and

immunogenicity.

Wheezing a possible issue.

Children with allergic reactions and asthma will need

exclusion.

Lab issues and pharmacopoeial

Extra SRIDs and calibrations on an already stressed

system.

The Bs seem to interfere with each other in lab tests

Adjuvants are v difficult

The upper fiducial limit will come into play for protein

Stability studies needed

Manufacturers.

They will need to start production before the

WHO rec is made and try and 2nd guess

2 strains.

A triple or quadruple Change one year there

will be practical difficulties.

SH more affected as time lines tighter.

Programme managers

Cost

If TIV and QIV out there will be marketing

issues

and perhaps conflicting advice.

Documents

Infants and Elderly: is your vaccine approved for these ... | Influenza vaccines in infants and elderly, 25 March 2014 Infants and Elderly: is your vaccine approved for these groups?