Development and serology based efficacy assessment of a trivalent foot-and-mouth disease vaccine Md. Al Amin 1 , M. Rahmat Ali 2 , M. Rafiul Islam, A.S.M. Rubayet Ul Alam 3 , Dipok Kumer Shill, M. Shaminur Rahman, Mohammad Anwar Siddique 4 , Munawar Sultana, M. Anwar Hossain 5,⇑ Department of Microbiology, University of Dhaka, Dhaka 1000, Bangladesh article info Article history: Received 10 March 2020 Received in revised form 25 May 2020 Accepted 27 May 2020 Available online 10 June 2020 Keywords: FMDV Trivalent vaccine Efficacy Serology abstract Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals throughout the world. The endemicity of this disease in Bangladesh has been causing high economic loss and an imped- iment to the full potential surge of livestock industries. In Bangladesh, vaccination using imported or locally produced FMD vaccines is the existing practice of controlling the disease, although vaccine failure cases are very common. Hence, to address the problem, the present study was envisaged to develop an effective FMD vaccine tailored to the circulating indigenous foot-and-mouth disease virus (FMDV) strains. Three local circulating FMDVs O/BAN/TA/Dh-301/2016 (MK088170.1 ), A/BAN/CH/Sa-304/2016 (MK088171.1 ) and Asia1/BAN/DH/Sa-318/2018 (MH457186.1 ) isolates were selected as vaccine strains based on recent epidemiology, genetic and antigenic analyses. These serotype O, A and Asia1 vaccine strains showed strong antigenic relationship (r1 > 0.3) with 100% to 75% of the respective circulating viruses. The candidate viruses were successfully inactivated by 3.0 mM binary ethylenimine within 7–10 h after the onset of inactivation. Extrapolation of inactivation kinetics confirmed < 1 log 10 TCID 50 in a 10000-liter batch liquid preparation after 24 h inactivation cycle. The inactivated virus particles were significantly (p < 0.05) concentrated and the trivalent vaccine was formulated using 6 mg per dose per ser- otype antigen payload. The trivalent vaccine was administered in divided doses in different groups of cat- tle. All doses of the vaccine elicited significantly (p < 0.05) higher levels of antibodies as early as 14-day post-vaccination (dpv) and peak antibody titers were achieved in 28 dpv. The ‘full dose’ (6.0 mg per dose per serotype) vaccine elicited antibody titers expected to confer protection in 100% cattle of the respec- tive group and maintained such level of antibodies beyond 180 dpv. Thus, the trivalent FMD vaccine pre- pared with 6.0 mg antigen per dose per serotype of the selected candidate viruses will confer protection against circulating FMDVs of Bangladesh and its neighboring countries. Ó 2020 Elsevier Ltd. All rights reserved. 1. Introduction Foot-and-mouth disease (FMD), an economically devastating and highly contagious vesicular disease, affects all types of domestic and wild cloven-hoofed animals including cattle, buffalo, sheep, goats, deer, and pigs [1]. Foot-and-mouth disease virus (FMDV), the etiological agent of the disease is a single-stranded positive-sense RNA virus belonging to the genus Aphthovirus and family Picornaviridae [2]. There are seven immunologically distinct serotypes of FMDV namely A, O, C, Asia1, SAT (Southern African Territories) 1–3. All the FMDV serotypes produce disease with same clinical manifestations but immunity to one serotype does not confer protection against another even some cases within the same serotypes due to the antigenic diversity [3,4]. FMD is endemic in Bangladesh causing huge economic losses per year{Chowdhury, 2015 #578}. The circulating FMDV serotypes in the country are- O (80–85%), A (10–15%) and Asia1 (up to 5%) [5]. Genetic diversity within the serotypes specifically in O and Asia1 are also present. Along with the previous sublineage Ind2001d, two novel sublineages Ind2001BD1 and Ind2001BD2 within the https://doi.org/10.1016/j.vaccine.2020.05.079 0264-410X/Ó 2020 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. E-mail address: hossaina@du.ac.bd (M.A. Hossain). 1 Present address: Quality Control Laboratory, Department of Livestock Services, Savar, Dhaka, Bangladesh. 2 Present address: Assistant Secretary, Ministry of Foreign Affairs, Dhaka, Bangladesh. 3 Present address: Department of Microbiology, Jashore University of Science and Technology, Jashore-7408, Bangladesh. 4 Present address: Northwestern University Feinberg School of Medicine, North- western University, Chicago, IL, USA. 5 Present address: Vice-Chancellor, Jashore University of Science and Technology, Jashore-7408, Bangladesh. Vaccine 38 (2020) 4970–4978 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine