title: A randomized non-inferiority clinical study to assess post-exposure prophylaxis by a new purified vero cell rabies vaccine (Rabivax-S) administered by intramuscular and intradermal routes.
abstract: Rabies is a 100% fatal disease but preventable with vaccines and immunoglobulins. We have developed a new purified vero cell rabies vaccine (Rabivax-S) and evaluated its safety and immunogenicity in post-exposure prophylaxis by intramuscular (IM) and intradermal (ID) routes.
  
  
  
  This was a randomized active-controlled non-inferiority study in 180 individuals (age 5years and above) with suspected rabies exposure (90 each with WHO Category II and Category III exposures). The participants received either Rabivax-S (1mL IM; five doses), Rabivax-S (0.1mL ID; eight doses) or purified chick embryo cell vaccine (PCEC, Rabipur®) (1mL IM; five doses). The IM doses were given on Day 0, 3, 7, 14 and 28 while the ID doses were given on days 0, 3, 7 and 28. Category III patients also received a human rabies immunoglobulin (HRIG) on Day 0. Adverse events (AEs) were recorded with diary cards till day 42. Rabies neutralizing antibody levels were measured on day 0, 7, 14, 28 and 42.
  
  
  
  In both the category II and III patients, the geometric mean concentration (GMC) ratios of Rabivax-S IM and Rabivax-S ID groups to PCEC IM were more than 1, thus proving the non-inferiority. GMCs were similar or higher in Rabivax-S groups at all the time points. Seroresponse against rabies (RFFIT titre⩾0.5IU/mL) was achieved in all participants. Mostly mild local and systemic adverse events were reported across the three groups and all resolved without sequelae.
  
  
  
  Rabivax-S was well tolerated and showed immunogenicity comparable to a licensed rabies vaccine by both IM and ID routes in post-exposure prophylaxis. Registry No.: CTRI/2012/11/003135.
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Bose
authors.affiliation: T.N. Medical College & BYL Nair Ch. Hospital, Mumbai, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Munshi
authors.affiliation: M.K.C.G. Medical College and Hospital, Berhampur, India.
authors.forename: Radha Madhab
authors.initials: RM
authors.lastname: Tripathy
authors.affiliation: National Institute of Mental Health and NeuroSciences (NIMHANS), Bangalore, India.
authors.forename: Shampur N
authors.initials: SN
authors.lastname: Madhusudana
authors.affiliation: Mandya Institute of Medical Sciences, Mandya, India.
authors.forename: B R
authors.initials: BR
authors.lastname: Harish
authors.affiliation: Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India.
authors.forename: Saket
authors.initials: S
authors.lastname: Thaker
authors.affiliation: Mandya Institute of Medical Sciences, Mandya, India.
authors.forename: B J
authors.initials: BJ
authors.lastname: Mahendra
authors.affiliation: Serum Institute of India Pvt. Ltd., Pune, India.
authors.forename: Bhagwat
authors.initials: B
authors.lastname: Gunale
authors.affiliation: Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India.
authors.forename: Nithya J
authors.initials: NJ
authors.lastname: Gogtay
authors.affiliation: Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India.
authors.forename: Urmila M
authors.initials: UM
authors.lastname: Thatte
authors.affiliation: National Institute of Mental Health and NeuroSciences (NIMHANS), Bangalore, India.
authors.forename: Reeta Subramaniam
authors.initials: RS
authors.lastname: Mani
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: K
authors.initials: K
authors.lastname: Manjunath
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Kuryan
authors.initials: K
authors.lastname: George
authors.affiliation: National Institute of Mental Health and NeuroSciences (NIMHANS), Bangalore, India.
authors.forename: Ashwin Belludi
authors.initials: AB
authors.lastname: Yajaman
authors.affiliation: Serum Institute of India Pvt. Ltd., Pune, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Sahai
authors.affiliation: Serum Institute of India Pvt. Ltd., Pune, India.
authors.forename: Rajeev M
authors.initials: RM
authors.lastname: Dhere
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Reginald G
authors.initials: RG
authors.lastname: Alex
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Debasis Das
authors.initials: DD
authors.lastname: Adhikari
authors.affiliation: Christian Medical College, Vellore, India.
authors.lastname: Abhilash
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Venkata
authors.initials: V
authors.lastname: Raghava
authors.affiliation: T.N. Medical College & BYL Nair Ch. Hospital, Mumbai, India.
authors.forename: Dipti
authors.initials: D
authors.lastname: Kumbhar
authors.affiliation: M.K.C.G. Medical College and Hospital, Berhampur, India.
authors.forename: Tapas Ranjan
authors.initials: TR
authors.lastname: Behera
authors.affiliation: Serum Institute of India Pvt. Ltd., Pune, India. Electronic address: drpsk@seruminstitute.com.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Kulkarni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D007194:India; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D056990:Post-Exposure Prophylaxis; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D014709:Vero Cells; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines; C532964:rabivax
keywords: Immunogenicity; Purified vero cell rabies vaccine; Rabies; Safety