title: A comparison of the tolerability of two dilution volumes (0.5 mL and 1.0 mL) of a purified chick embryo cell rabies vaccine administered intramuscularly to healthy adult volunteers: A randomized, intraindividual, assessor-blind study.
abstract: BACKGROUND
  The current recommendation of the manufacturer for administering purified chick embryo cell rabies vaccine (PCECV) is to reconstitute the contents with 1.0 mL of water for injection (WFI). However, it has been debated whether a lower volume of WFI (0.5 mL) is likely to cause less pain.
  
  
  OBJECTIVE
  The aims of this study were to compare the tolerability of PCECV administered IM at a volume of 0.5 mL versus 1.0 mL of diluent and to determine the immunogenicity of the vaccine when administered according to the World Health Organization-recommended preexposure prophylaxis regimen for rabies immunization.
  
  
  METHODS
  This comparative, intraindividual, assessor-blind study was conducted at the Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital Mumbai, India). Healthy volunteers aged 18 to 50 years received, by randomized sequence, 3 IM injections of PCECV, diluted in 0.5 mL or 1.0 mL of WFI, on study days 0, 7, and 28. Tolerability was assessed at 30 minutes and 24 hours after injection and included assessments for local and systemic reactions. For immunogenicity assessment, rabies virus-neutralizing antibody 0RVNA) titers were assayed at baseline and on day 49 (ie, 3 weeks after the third injection).
  
  
  RESULTS
  Twenty-six subjects (24 men, 2 women; mean [SD] age, 22.4 [2.4] years; mean [SD] body weight, 59.0 [11.3] kg) entered the study. Twenty-five subjects were included in the tolerability assessment; 24 in the immunogenicity assessment. No statistically significant differences were found between dilutions in the frequency of local and systemic reactions. Most reactions were mild. All subjects developed RVNA titers >0.5 IU/mL (indicative of protection) by day 49.
  
  
  CONCLUSIONS
  In this population of healthy volunteers, a full antigenic dose of PCECV in a dilution of 0.5 mL WFI is as well tolerated locally and systemically as in a dilution of 1.0 mL. All subjects developed levels of RVNA far exceeding 0.5 IU/mL, which is indicative of protection against rabies.
authors.affiliation: Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Kulkarni
authors.affiliation: Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai, India.
authors.forename: Urmila
authors.initials: U
authors.lastname: Thatte
authors.affiliation: Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Shinde
authors.affiliation: Department of Clinical Pharmacology, Topiwala National Medical College and Bai Yamunabai Laxman Nair Charitable Hospital, Mumbai, India.
authors.forename: Shalaka
authors.initials: S
authors.lastname: Dharadhar
authors.affiliation: Clinical Research and Medical Affairs, Chiron Vaccines, Siena, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Popova
authors.affiliation: Clinical Research and Medical Affairs, Chiron Vaccines, Mumbai, India.
authors.forename: Hoshang
authors.initials: H
authors.lastname: Vakil
keywords: immunogenicity; purified chick embryo cell rabies vaccine; rabies vaccine; tolerability; volunteer