Induction of Antibodies and T Cell Responses by a Recombinant Influenza Virus Carrying an HIV-1 TatΔ51-59 Protein in Mice

被引:3
作者
Garulli, B. [1 ,2 ]
Di Mario, G. [1 ]
Stillitano, M. G. [1 ]
Compagnoni, D. [3 ]
Titti, F. [3 ]
Cafaro, A. [3 ]
Ensoli, B. [3 ]
Kawaoka, Y. [4 ,5 ,6 ,7 ]
Castrucci, M. R. [1 ]
机构
[1] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy
[2] Univ Roma La Sapienza, Dept Biol & Biotechnol Charles Darwin, I-00185 Rome, Italy
[3] Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy
[4] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53711 USA
[5] Univ Tokyo, Inst Med Sci, Div Virol, Dept Microbiol & Immunol, Tokyo 1088639, Japan
[6] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Tokyo 1088639, Japan
[7] Exploratory Res Adv Technol, Infect Induced Host Responses Project, Saitama 3320012, Japan
关键词
IMMUNE-RESPONSES; TAT PROTEIN; CYNOMOLGUS MONKEYS; REVERSE GENETICS; VIRAL LOAD; MUCOSAL; IMMUNODEFICIENCY; VACCINE; INFECTION; ANTIGEN;
D O I
10.1155/2014/904038
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Recombinant influenza viruses hold promise as vectors for vaccines to prevent transmission of mucosal pathogens. In this study, we generated a recombinant WSN/Tat Delta(51-59) virus in which Tat protein lacking residues 51 to 59 of the basic domain was inserted into the N-terminus of the hemagglutinin (HA) of A/WSN/33 virus. The Tat Delta(51-59) insertion into the viral HA caused a 2-log reduction in viral titers in cell culture, compared with the parental A/WSN/33 virus, and severely affected virus replication in vivo. Nevertheless, Tat-specific antibodies and T cell responses were elicited upon a single intranasal immunization of BALB/c mice with WSN/Tat Delta(51-59) virus. Moreover, Tat- specific immune responses were also detected following vaccine administration via the vaginal route. These data provide further evidence that moderately large HIV antigens can be delivered by chimeric HA constructs and elicit specific immune responses, thus increasing the options for the potential use of recombinant influenza viruses, and their derivatives, for prophylactic and therapeutic vaccines.
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