Immunogenicity of 2-dose pre-exposure rabies vaccine co-administered with quadrivalent influenza vaccine in children.

OBJECTIVES: The World Health Organization recommends a 2-dose rabies pre-exposure prophylaxis (PrEP) regimen. This study aimed to compare the immunogenicity of rabies PrEP regimens co-administered with inactivated quadrivalent influenza vaccine (IIV4). METHODS: Children aged 3 to 9 years were randomly assigned (2:2:1) to receive 0.25 mL of chromatographically purified Vero cell rabies vaccine intramuscularly: Group A at day 0, 7 with IIV4; Group B at day 0, 28 with IIV4; Group C at day 0, 7. A booster-dose of CPRV was given on day 365. Primary outcome was the proportion of children with protective rabies virus neutralizing antibody (RVNA) ≥ 0.5 IU/mL, on day 42 and 7 days post-booster. RESULTS: From November 2019 to January 2020; 100 children with a median age (IQR) of 5.4 years (4.8-7.3) were enrolled. All participants achieved protective RVNA titers on day 42 and 7-days post booster. Geometric mean titers (GMT) at day 42 were Group A, 8.98(95%CI 7.06-11.42); Group B, 23.89(95%CI 19.33-29.51); Group C, 9.94(95%CI 7.03-14.06). Likewise, RVNA GMT at 7 days post-booster were Group A, 42.53(95%CI 18.41-66.64); Group B, 23.19(95%CI 17.28-29.10); Group C, 57.75 (95%CI 35.86-79.67). CONCLUSIONS: The 2-dose PrEP regimen of rabies vaccine produces adequate immune response either 0,7 or 0, 28 regimens.

Immunogenicity and safety of WHO-approved TRC-ID regimen with a chromatographically purified Vero cell rabies vaccine with or without rabies immunoglobulin in children.

INTRODUCTION: Children are at risk of rabies exposure in many Asian countries. The safety and immunogenicity profile of the WHO-approved two-site intradermal Thai Red Cross regimen (modified TRC-ID regimen; 2-2-2-0-2) with a new chromatographically purified Vero-cell rabies vaccine (CPRV) is lacking. Area covered: We studied the safety and immunogenicity of the TRC-ID regimen with a new CPRV in non-immunized Thai children with possible or proven rabies exposure. Thirty-nine seronegative patients (age range 2-14 years) with rabies exposure (WHO categories II or III) received two 0.1-mL intradermal doses of CPRV at both deltoid regions on days 0, 3, 7, and 28. Twenty-five patients (64.1%) received rabies immunoglobulin due to having rabies exposure, according to WHO category III. All serum samples were tested for rabies neutralizing antibody (Nab) by the rapid fluorescent focus inhibition test (RFFIT) before vaccination, and on days 14 and 90 after vaccination. All patients had an adequate immune response (Nab titers ≥ 0.5 IU/mL) on days 14 and 90. No patients died of rabies infection. No serious adverse reactions were observed. Expert commentary: CPRV is economic, safe, and immunogenic if given as the modified TRC-ID regimen in children.

New method to produce equine antirabies immunoglobulin F(ab')2 fragments from crude plasma in high quality and yield.

Rabies is still a major cause of human deaths in several developing countries. According to the World Health Organization, administration of antirabies serum or antirabies immunoglobulin is recommended for patients who have experienced a category-III exposure to rabies. Improvement of antirabies immunoglobulin production is required to enhance safety and efficacy of the products. In this paper, a new method to produce equine antirabies immunoglobulin F(ab')(2) fragments from crude plasma is proposed. First, protein G affinity chromatography was used to purify IgG from equine plasma. Moreover, purification of IgG was shown to facilitate its digestion by pepsin. Compared to the direct digestion of crude plasma, a lower amount of pepsin and a shorter digestion time were required to completely digest the purified IgG to F(ab')(2). Complete digestion of purified IgG to F(ab')(2) was achieved at a pepsin/IgG (w/w) ratio of 5:45 with preservation of structure and potency. Finally, purification of F(ab')(2) was accomplished by a combination of protein A affinity chromatography and ultrafiltration with a 50-kDa nominal molecular weight cut-off membrane. The new process resulted in 68.9±0.6 (%) total recovery of F(ab')(2) and a F(ab')(2) product of high potency.