Filippo Ansaldi Di.S.Sal., University of Genoa

I.R.C.C.S. “A.O.U. San Martino-IST”, Genoa

Weller TH, 1948

Boger WP, 1957

McCarroll JR, 1958

Klein M, 1961

McElroy JT, 1969

Phillips CA, 1970

Foy HM, 1970

Marks MI, 1971

Brown H, 1977

Brooks JH, 1977

Halperin W, 1979

Herbert FA, 1979

Kenney RT, 2004

Auewarakul P 2007

Manuel O, 2007

Chiu SS, 2007;

Sugimura T, 2008

Kunzi V, 2009

Chiu SS, 2009

Gelinck LB, 2009

Jo YM, 2009

Chuaychoo B, 2010 …

Acceptability Higher Immune response [HR and LR, Ag sparing]

Logistics

Depth and volume consistency Pain

Skilled personnel

Sticchi L et al., JPMH 2010

Jet Injectors

Microneedle

Soluvia Microinjection system

18-59 years1

18-64 years2 60 years1

To improve acceptability

and coverage

Intanza® 9 mcg1

Fluzone ® Intradermal2

Intanza® 15 mcg

To improve immunogenicity,

efficacy and effectiveness

-12 -8 -4 0 4 8 12

18-60 year, N.R.R.T., 15 mcg ID vs 15 mcg IM (Morel2010)

>60 years, 15 mcg ID vs 15 mcg Vir-IM (Ansaldi in press)

>65 years, 15 mcg ID vs 15 mcg MF59 IM (Vandamme 2010)

>60 years, 15 mcg ID vs 15 mcg IM (Arnou 2009)

>60 years, 21 mcg ID vs 15 mcg IM (Holland 2008)

>60 years, 15 mcg ID vs 15 mcg IM (Holland 2008)

18-60 years, HIV+, 9 mcg ID vs 15 mcg IM (Ansaldi 2012)

18-60 yers, 9 mcg ID vs 15 mcg IM (Arnou 2010)

20-59 years, 9 mcg ID vs 15 mcg IM (Beran 2009)

19-58 years, 9 mcg ID vs 15 mcg IM (Beran 2009)

18-57 years, 6 mcg ID vs 15 mcg IM (Beran 2009)

18-57 years, 9 mcg ID vs 15 mcg IM (Leroux 2008) Shivering

Malaise

Fever >38°C for >24 h

Inject.-site ecchymosis

Inject.-site induration > 5 cm

ID-IM Difference in cumulative incidence rates (%)

Ansaldi F et al., Expert Opinion 2011 (modified)

-10 0 10 20 30 40 50 60

Ecchymosis

Induration

Erythema

Pruritus

Pain

At least one

Solicited injection site reaction (days 0-7)

Shivering

Mialgia

Malayse

Headache

Fever

At least one

Solicited systemic reaction (days 0-7)

Arnou R et al., Vaccine 2009

ID-IM Difference in cumulative incidence rates (%)

0

5

10

15

20

25

D0 D1 D2 D3 D4 D5 D6 D7 D0 D1 D2 D3 D4 D5 D6 D7

Mild

Moderate

Severe

Durando P et al., Adv Ther 2012

Pre

vale

nce

(%

)

ID IM

Durando P1, Alberti M1, Pintaudi A1, Accurso G1, Rosselli R 2, Turello V 2, Marensi L 2, Ansaldi F1, Sticchi L1, Corsini D 3, Icardi G1, and the Intradermal

Influenza Vaccine Study Group* [de Florentiis D1]

*Intradermal Influenza Vaccine Study Group: Albanese E, Alicino C, Angeli C, Arenare L, Borzone F, Cacciani R, Cardamone G, de Florentiis D, …

1Department of Health Sciences, San Martino Hospital, University of Genoa, Genoa, Italy 2Local Public Health Unit of Genoa (ASL 3 Genovese), Genoa, Italy 3Informa Srl, Rome, Italy

Figure 1. How acceptable

was/were your local reaction(s)?

Figure 2. How acceptable was

your pain?

Figure 3. How satisfied were you

with the injection system?

Not at all

A little

Moderately

Very

Totally

Satisfied:

99.6% Acceptable:

98.8%

Acceptable:

98.4% Acceptable:

97.3%

-6 -3 0 3 6 9

>65 years, 15 mcg ID vs 15 mcg MF59 IM (Van Damme2010)

18-60 year, N.R.R.T., 15 mcg ID vs 15 mcg IM (Morel2010)

>60 years, 15 mcg ID vs 15 mcg Vir.-IM (Ansaldi in press)

>60 years, 15 mcg ID-ID-ID vs 15 mcg IM-IM-IM (Arnou 2009)

>60 years, 15 mcg ID-ID vs 15 mcg IM-IM (Arnou 2009)

>60 years, 15 mcg ID vs 15 mcg IM (Holland 2008)

18-60 years, HIV+, 9 mcg ID vs 15 mcg IM (Ansaldi 2012)

18-64 years, 9 mcg ID vs 15 mcg IM (Frenck 2011)

18-60 years, 9 mcg ID vs 15 mcg IM (Arnoui 2010)

20-59 years, 9 mcg ID vs 15 mcg IM (Beran 2009)

19-58 years, 9 mcg ID vs 15 mcg IM (Beran 2009)

18-57 years, 9 mcg ID vs 15 mcg IM (Leroux 2008)

H1N1H3N2B

Ansaldi F et al., Expert Opinion 2011

ID-IM Difference in MFI

-10 0 10 20 30

18-60 years, N.R.R.T., 15 mcg ID vs 15 mcg IM (Morel2010)

>60 years, 15 mcg ID vs 15 mcg Vir.-IM (Ansaldi in press)

>60 years, 15 mcg ID-ID-ID vs 15 mcg IM-IM-IM (Arnou 2009)

>60 years, 15 mcg ID-ID vs 15 mcg IM-IM (Arnou 2009)

>60 years, 15 mcg ID vs 15 mcg IM (Arnou 2009)

18-60 years, HIV+, 9 mcg vs 15 mcg IM (Ansaldi 2012)

18-64 years, 9 mcg ID vs 15 mcg IM (Frenck 2011)

18-60 years, 9 mcg ID vs 15 mcg IM (Arnou 2010)

20-59 years, 9 mcg ID vs 15 mcg IM (Beran 2009)

19-58 years, 9 mcg ID vs 15 mcg IM (Beran 2009)

18-57 years, 9 mcg ID vs 15 mcg IM (Leroux 2008)H1N1

H3N2

B

Ansaldi F et al., Expert Opinion 2011

ID-IM Difference in seroprotection rates (%)

1 Ansaldi F et al., Vaccine 2012 2 Ansaldi F et al., Human Vaccin 2013

Aim. To evaluate the ability of intradermal influenza vaccine to elicit an effective antibody

response against circulating A(H3N2) and A(H1N1)pdm09 viruses presenting different

antigenic pattern respect to that of vaccine strains.

Season 2006/071 2010/112

ID versus Split Virosomal

Popolation ≥ 60 years, 50 participants ≥ 60 years, 55 participants

Vaccine strain A/Wisconsin/67/2005 (H3N2) A/California/7/2009 (H1N1) pdm 09

Immunogenicity

evaluated

against

A/Wisconsin/67/2005 (H3N2) A/California/7/2009 (H1N1) pdm 09

A/Brisbane/10/07 (H3N2)

A(H3N2) strains circulating during the

2005/06 and 2006/07 seasons

A(H1N1) pdm 09 strains circulating

during the 2010/11 season

Timing 0; 21 days 0; 28 and 90 days

Assays HI and NT HI and NT

Brisbane/07-like

Nepal/06-like-like

California/04-like

Wisconsin/05

Perth/10-like

Stockh/10-like

Christch/10-like

S.Carol/10-like

Split-IM ID Virosome-IM

MF

I

Ser

oco

nve

rsio

n

Ser

op

rote

ctio

n

MF

I

Ser

oco

nve

rsio

n

Ser

op

rote

ctio

n

MF

I

Ser

oco

nve

rsio

n

Ser

op

rote

ctio

n

Wisc/05 (H3N2)

Genoa/62/05

Genoa/3/07

Brisb/07

Genoa/3/06

Genoa/2/07

Cal/09 (H1N1)

Genoa/1/11

Genoa/6/11

Genoa/24/11

IM vaccine

ID vaccine

5

10

20

40

80

160

5

10

20

40

80

160

Pos

t vac

cina

tion

GM

T (

95%

C.I.

)

California/04 clade Nepal/06 clade Brisbane/07 clade Ansaldi F et al., Vaccine 2012

0

1

2

3

4

5

Wilcoxon test p<0.05

IM vaccine

ID vaccine

75° percentile

Median

25° percentile

Ansaldi F et al., Vaccine 2012

Beyer et al., Virus Research 2004

160

80

40

20

10

5

Cor

rect

ed p

ost v

acci

natio

n H

I tite

r

IM vaccine

ID vaccine

5

10

20

40

80

160

5

10

20

40

80

160

Pos

t vac

cina

tion

GM

T (

95%

C.I.

)

Wilcoxon test p<0.05

Wilcoxon test p=0.05 Ansaldi F et al., Vaccine 2012

5

10

20

40

80

160

5

10

20

40

80

160

Virosomal IM

ID

Pos

t vac

cina

tion

GM

T (

95%

C.I.

)

Wilcoxon test p<0.05 Ansaldi F et al., Human Vaccin 2013

1 month after vaccination 3 month after vaccination Perth/10

Stockh/10

Christch/10 S.Carol/10

ID vaccination offers potential advantages compared with IM or SC

routes regarding acceptability, immune response and logistical aspects

Three ID formulations using Soluvia device are approved and available

on the market : Intanza ® 9 μg and 15 μg and Fluzone® ID [9 μg]

Licensed ID vaccines are safe and immunogenic. The injection-site

reactions are very well accepted and are generally not a cause for

concern. The level of satisfaction with the ID microinjection system

was high, as was the willingness to be vaccinated the following year.

Intanza® 15 μg induces a higher immune response than IM vaccine in

the elderly against vaccine strains

Several immune response parameters assessed against circulating

viruses both by HI and NT assays were significantly higher in subjects

immunized with ID vaccine than with the IM or Virosomal vaccine

ID vaccination elicited broader antibody responses against

heterogeneous A(H3N2) and A(H1N1)pdm 09 strains in the elderly

than IM vaccination.