Safety and immunogenicity of a glycoprotein E gene-deleted bovine herpesvirus 1 strain as a candidate vaccine strain

Weiss, Marcelo; Anziliero, Deniz; Martins, Mathias; Weiblen, Rudi; Flores, Eduardo Furtado

doi:10.1590/S0100-736X2016001100002

Marcelo Weiss

Universidade do Oeste de Santa Catarina (Unoesc), Rua Dirceu Giordani 696, Xanxerê, SC 89820-000, Brazil.

Deniz Anziliero

Faculdade Meridional (Imed), Rua Senador Pinheiro 304. Passo Fundo, RS 99070-220, Brazil.

Mathias Martins

Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, prédio 63ª, Santa Maria, RS 97105-900, Brazil.

Rudi Weiblen

Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, prédio 63ª, Santa Maria, RS 97105-900, Brazil.

Eduardo Furtado Flores ^**Corresponding author: eduardofurtadoflores@gmail.com

Setor de Virologia, Departamento de Medicina Veterinária Preventiva, Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, prédio 63ª, Santa Maria, RS 97105-900, Brazil.

*Corresponding author: eduardofurtadoflores@gmail.com

Figures (3)
Tables (4)

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Fig.1:
Body temperature of calves of the challenge test. Six animals were vaccinated with a BoHV-1gEΔ virus and 47 days later were challenged with a heterologous virulent BoHV-1 strain. Four calves were kept as controls. Dotted line marks the threshold for fever. Bars represent the mean standard error.

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Fig.2:
Virus shedding in nasal swabs collected from calves of the challenge test. Mean virus titers for each group (vaccinated, controls) expressed in log₁₀ TCID₅₀/ml. Six animals were vaccinated with a BoHV-1gEΔ virus and 47 days later were challenged with a heterologous virulent BoHV-1 strain. Four calves were kept as controls. Bars represent the mean standard error.

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Fig.3:
Clinical score of the challenge test. Six calves were vaccinated with BoHV-1gEΔ and 47 days later were challenged with a heterologous virulent BoHV-1 strain. Four calves were kept as controls. Bars represent the mean standard error.

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Table 1:
Results of the safety test. Clinical, virological and serological findings in calves inoculated intramuscularly with the recombinant BoHV-1gEΔ and monitored during the acute phase and after dexamethasone (Dx) administration

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Table 2:
Results of the immunogenicity test using live virus. Serological response of calves vaccinated with live recombinant BoHV-1gEΔ and tested for virus neutralizing and gE antibodies at day 42 post-vaccination

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Table 3:
Results of the immunogenicity test using inactivated virus. Serological response of calves vaccinated twice with inactivated, adjuvanted BoHV-1gEΔ and tested for virus neutralizing and gE antibodies at day 60 post-vaccination (30 days after the second vaccine dose)

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Table 4:
Serological response of calves immunized with the recombinant BoHV-1gEΔ and challenged intranasally with a heterologous, virulent BoHV-1 strain at day 47 post-vaccination

Treatment	Animal #	Virus shedding/ clinical	Acute infection				Virus shedding/ sclinical	Dexametasone treatment
			VN antibodies^a		Anti-gE ELISA^b			VN antibodies	Anti-gE ELISA
			D0pi^c	D47pi	D0pi	D47pi		D14 pDx^d	D14pDx
BoHV-1gEΔ	117	-^e	<1^f	2	-^g	-	-	1	-
108.5TCID50/animal	127	-	<1	2	-	-	-	3	-
Intramuscular	129	-	<1	3	-	-	-	3	-
	132	-	<1	4	-	-	-	3	-
	136	-	<1	2	-	-	-	3	-
				GMT:2.6^h				GMT:2.6
Control animals	118	-	<1	<1	-	-	-	<1	-
Control animals	135	-	<1	<1	-	-	-	<1	-

Treatment	Animal #	VN antibodies^a		Anti-gE antibodies^b
Treatment	Animal #	Day 0	Day 42pv^c	Day 42pv
Group I	101	<1^d	3	-^e
BoHV-1gEΔ	102	<1	3	-
10^7.3TCID₅₀/animal	104	<1	1	-
Intramuscular	105	<1	2	-
	106	<1	2	-
	107	<1	3	-
	108	<1	1	-
	109	<1	1	-
			GMT: 2a^f
Group II	5	<1	2	-
BoHV-1gEΔ	76	<1	2	-
10^7.3TCID₅₀/animal	89	<1	1	-
Subcutaneous	99	<1	2	-
	152	<1	1	-
	154	<1	2	-
	157	<1	2	-
	158	<1	1	-
	166	<1	2	-
			GMT: 1.65a
Group III	112	<1	1	+^g
BoHV-1 SV56/90	113	<1	2	+
10^7.3TCID₅₀/animal	114	<1	2	+
Intramuscular			GMT: 1.65a^h

Treatment	Animal #	VN titers^a		Anti-gE antibodies^b
Treatment	Animal #	Day 0	Day 60^cpv^d	Day 60pv
Group IV	2	<1^e	2	-^f
BoHV-1gEΔ	30	<1	2	-
10^7.3TCID₅₀/animal	50	<1	1	-
Subcutaneous	54	<1	2	-
Subcutaneous	71	<1	2	-
Adjuvant: Aluminum hydroxide	74	<1	2	-
	87	<1	3	-
	95	<1	3	-
Two vaccine doses at 30 days interval	96	<1	3	-
	98	<1	4	-
	119	<1	3	-
	121	<1	3	-
	125	<1	2	-
			GMT: 2.45a^g	-
Group V	1	<1	4	-
BoHV-1gEΔ	3	<1	3	-
10^7.3TCID₅₀/animal	8	<1	4	-
Subcutaneous	9	<1	4	-
Subcutaneous	11	<1	4	-
Adjuvant: Montanide^™ Gel 1	22	<1	3	-
	35	<1	2	-
	58	<1	5	-
Two vaccine doses at 30 days interval	61	<1	7	-
	62	<1	4	-
	78	<1	1	-
	85	<1	5	-
	88	<1	5	-
	120	<1	4	-
			CMT: 3.9^b

Treatment	Animal #	Post-vaccination (pv)				Post-challenge (pc)
		VN titer^a		Anti-gE antibodies^b		VN titer		Anti-gE antibodies
		D0	D47pv	D0	D47pv	D30pc	D90pc	D30pc	D90pc
Immunized	109	<1^c	2	-^d	-	4	2	+^e	+
BoHV-1gEΔ	130	<1	2	-	-	6	3	+	+
10^7.5TCID₅₀/animal	131	<1	3	-	-	7	4	+	+
Intramuscular	134	<1	2	-	-	5	3	+	+
	139	<1	2	-	-	4	1	+	+
	142	<1	1	-	-	7	5	+	+
			GMT: 2^f			GMT: 5.5 .2	GMT: 3
Control animals	01	<1	<1	-	-	2	5	+	+
	03	<1	<1	-	-	1	2	+	+
	108	<1	<1	-	-	3	2	+	+
	105	<1	<2	-	-	2	5	+	+
						GMT: 2	GMT: 3.5

[1] *Corresponding author: eduardofurtadoflores@gmail.com

Brasil

Brasil

Safety and immunogenicity of a glycoprotein E gene-deleted bovine herpesvirus 1 strain as a candidate vaccine strain

Atenuação e imunogenicidade de uma cepa recombinante do herpesvírus bovino tipo 1 defectiva na glicoproteína E

ABSTRACT: