LONG TERM IMMUNOGENICITY OF ABHAYRAB

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

2. Persistence of neutralizing antibody in
previously vaccinated subjects: Multiple
studies showing long lasting immunity
with ABHAYRAB
“Impact on rabies immunization practice…”
DR. B N PATNAIK, MD
Head clinical Development
INDIA

3. 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.

4. Initial Abhayrab studies…
Class of No. of Abhayrab ERIG Ab titres
Bite Subjects schedule on
Group I Healthy 60 Days 0, 7 Not given Days 0,14,35
volunteers and 21 and 365
Group II Category II 75 Days 0, 3, 7, Not given Days 0, 14,
14,30 and 90 30, 90 and
365
Group III Category III 67 Days 0, 3, 7, Not given Days 0, 14,
14,30 and 90 30, 90 and
365
Group IV Category III 88 Days 0, 3, 7, Given Days 0, 14,
14,30 and 90 30, 90 and
365
Published by Elsevier Ltd in 2004
Conducted by :Institute of Preventive Medicine, Narayanguda, Hyderabad,
Pasteur Institute of India, Connor, Tamilnadu, India

5. Persistence of Ab over time
20
19
18 18.19
17 GROUP I
16
15.78
15 15.03 GROUP II
14
13
13.53 GROUP III
12.69 12.26
12
11.66 GROUP IV
GMT
11
10 10.34
9
9.47
8 8.04 8.42
7.82
7 7.04
6
5.8
5
4 4.15
3
2
1
0.61
0.83 0.78
0 0
0 7 14Days 35 90 365

6. 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

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

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

9. 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

10. 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 No. of GMT Value, IU
dose of Patients Mean Range
vaccine
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

11. 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

12. Rabies Virus Neutralizing Antibody (RVNA)
Concentration by age group
Characteristics n = 101 people
≤ 15 years old > 15 years old
No. of subjects 26 75
RVNA GMT 95 % CI GMT 95 % CI
48 to >53 Week 2.06 ± 1.14 1.97 ± 1.19
Antibody concentration in the age ≤ 15 years old higher than
the age >15 not but not statistically significant( P>0.05)

13. Antibody concentrations over time from first dose
to evaluation weeks
ANTIBODY CONCENTRATION
TIME
(IN WKS AFTER FIRST TOTAL
DOSE) 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

14. 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)

15. Antibody titers
GMT (IU/mL) (%) of Subjects Seroconverted
Abhayrab Rabipur Abhayrab Rabipur
Vaccine Vaccine Vaccine Vaccine
Pre vaccination
0.12 (42) 0.10 (50) -- --
Day 0 (N)
(0.00, 0.48) (0.00,0.40)
Range (Min, Max)
Post Vaccination
Day 38 (N) 60.39 (42) 56.55 (50) 100 100
Range (Min, Max) (10.81, 247.66) (70.14, 247.66)
Day 365 (N) 0.94 (25) 1.15 (25) 100 100
Range (Min, Max) (0.54, 3.09) (0.56, 4.03)

16. SEROPROTECTION

17. 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.

18. 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

19. 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…..

20. THANKS