RABIES FREE WORLD………the one who needs the most

DR. B N PATNAIK, MDHead clinical Development

INDIA

Persistence of neutralizing antibody in previously vaccinated subjects: Multiple studies showing long lasting immunity

with ABHAYRAB

“Impact on rabies immunization practice…”

In the absence of PEP vaccination it is assumed that just under 20% of victims of bites by rabid animals develop

rabies and that all clinical cases of human rabies result in death(1).

Incomplete PEP vaccination is less effective and almost 10% of human rabies cases reported from India had received incomplete PEP vaccination with CCVs (2)

 

1. Shim E, Hampson K, Cleaveland S, Galvani AP (2009) Evaluating the cost-effectiveness of rabies post-exposure

prophylaxis: a case study in Tanzania. Vaccine 27: 7167–7172

2. Sudarshan MK, Madhusudana SN, Mahendra BJ, Rao NSN, Ashwath Narayana DH, et al. (2007) Assessing the burden of

human rabies in India: results of a national multi-center epidemiological survey. International Journal of Infectious Diseases

11: 29–35.

Initial Abhayrab studies…

Class of Bite

No. of Subjects

Abhayrab schedule

ERIG Ab titres on

Group I Healthy volunteers

60 Days 0, 7 and 21

Not given Days 0,14,35 and 365

Group II Category II 75 Days 0, 3, 7, 14,30 and 90

Not given Days 0, 14, 30, 90 and

365

Group III Category III 67 Days 0, 3, 7, 14,30 and 90

Not given Days 0, 14, 30, 90 and

365

Group IV Category III 88 Days 0, 3, 7, 14,30 and 90

Given Days 0, 14, 30, 90 and

365

Published by Elsevier Ltd in 2004Conducted by :Institute of Preventive Medicine, Narayanguda, Hyderabad, Pasteur Institute of India, Connor, Tamilnadu, India

Persistence of Ab over time

0

12.69

18.19

12.26

00.83

13.53

15.03

7.04

4.15

00.78

15.78

8.04

9.47

7.82

0

0.61

10.34

11.66

8.42

5.8

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

0 7 14 35 90 365

GM

T

Days

GROUP I

GROUP II

GROUP III

GROUP IV

Multi-centric study on the use of intradermal administration of tissue

culture antirabies vaccines in India

Methods:

Healthy volunteers selected from five centres in the country.

The TCARVs used for intradermal administration were Purified Vero cell Rabies vaccine (PVRV Abhayrab and Coonoor), Purified chicken embryo cell vaccine (PCEC Rabipur) and Purified duck embryo vaccine ( PDEV Vaxirab) with a 2-2-2-0-1-1 regimen.

Responses to intradermal TCARVs were compared with that of French PVRV (Aventis) administered intramuscularly on 0, 3, 7,14 and 28 days.

Ten volunteers were recruited for each of the TCARV arm in each center as well as for control group receiving French PVRV.

Blood samples were collected on days 14, 28, 90 and 180 days

Study done by : Indian Council of Medical Research

Sero-protection rate, GMTs, of Anti-Rabies antibodies and its 95% CI among the volunteers receiving different TCRVs

Sero-protection rate, Geometric mean titers of anti-rabies antibodies an ICMR Study

IMMUNOGENECITY OF PURIFIED VERO CELL RABIES VACCINE USED IN THE TREATMENT OF FOX-BITE

VICTIMS IN INDIA

• 19 Patients aged 6-70 years

• Category III fox bites

• Abhayrab was administered IM to all on days 0,3,7,14 and 28

• 6 patients were treated with equine rabies antiserum (Central research institute)

• 11 patients were administered abhayrab booster on day 1020 after the first dose

• Blood was collected for antibody titre estimation on days 30,90,870,1020, and 1050

Study by Dr. I S Matha of district hospital Nasik and Dr.S R Salunke of Directorate of health services ,Mumbai,India

Response to a booster vaccination on day 1020 after the first dose of vaccine in patients who had received

either vaccine alone or vaccine + ERIG

Days after 1st dose of vaccine

No. of Patients

GMT Value, IU

Mean Range

30 12 3.16 1.00 – 8.00

90 16 25.00 8.00 – 64.00

870 11 0.77 0.26 – 2.10

1020 11 0.48 0.11 – 2.00

1050 11 30.08 2.57 – 69.18

REVIEW OF EXISTING ANTIBODIES IN TREATED POST-EXPOSURE BY CELL CULTURE VACCINES: ABHAYRAB ( IM )REGIMEN

ONE YEAR FROM THE FIRST INJECTIONS (VIETNAM)

PRINCIPAL INVESTIGATOR:

PROF ĐINH KIM XUYẾN, PhD DEPUTY DIRECTOR OF CENTER FOR SCIENTIFIC RESEARCH FOR CUMMUNITY HEALTH,HANOI,VIETNAM

Rabies Virus Neutralizing Antibody (RVNA)

Concentration by age group

Characteristics n = 101 people

≤ 15 years old > 15 years old

No. of subjects 26 75

RVNA48 to >53 Week

GMT2.06

95 % CI± 1.14

GMT1.97

95 % CI± 1.19

Antibody concentration in the age ≤ 15 years old higher than the age >15 not but not statistically significant( P>0.05)

Antibody concentrations over time from first dose to evaluation weeks

TIME

(IN WKS AFTER FIRST DOSE)

TOTAL

ANTIBODY CONCENTRATION

0.5-1 1.1-5 >5

48-50 22 5 9 5

51-53 29 10 12 6

>53 69 25 21 8

Total 120 40 42 19

Study to compare the safety and immunogenicity of Abhayrab with commercially available Rabipur vaccine, both administered as per updated Thai

Regimen (2-2-2-0-2) in healthy volunteers (simulated post-exposure study)

Antibody titers GMT (IU/mL)

(%) of Subjects Seroconverted

Abhayrab Vaccine

Rabipur Vaccine

Abhayrab Vaccine

Rabipur Vaccine

Pre vaccination Day 0 (N) Range (Min, Max)

0.12 (42) (0.00, 0.48)

0.10 (50) (0.00,0.40)

-- --

Post Vaccination Day 38 (N) Range (Min, Max)

60.39 (42) (10.81, 247.66)

56.55 (50) (70.14, 247.66)

100 100

Day 365 (N) Range (Min, Max)

0.94 (25) (0.54, 3.09)

1.15 (25) (0.56, 4.03)

100 100

SEROPROTECTION

Implications…….

• Reduced PrEP regimens would reduce the cost of protecting vulnerable populations against rabies and would promote better compliance.

• thus supporting opportunities to conduct mass PrEP rabies vaccination in children, the population most at risk of dying of this dreaded disease.

Implication……

• (PVRV) administered as a pre- or post-exposure series will provide very long lasting immune memory in normal host recipients.

• Two intradermal booster injections on days 0 and 3 will result in an accelerated anamnestic neutralizing antibody response and obliviate the need for rabies immunoglobulin in the event of a new exposure

K. Suwansrinon et al. / Vaccine 24 (2006) 3878–3880

Possible Future !!

Inclusion of Intradermal PVRV in EPI (Along with DTP vaccine schedule) of developing/Rabies Endemic countries..

Large CTs to validate the number and age for boosters

We can possibly keep Rabies related Death to a minimum…..

THANKS