HIV-1CN54 DNA疫苗滴鼻免疫小鼠诱发系统和黏膜免疫应答

目的：探讨重组痘苗病毒rVVsyngp120或rVVmCN54gp120候选疫苗是否增强HIV-1CN54合成gp120基因(syngp120)DNA疫苗的免疫原性。方法：第0、7、14、21天用DNA疫苗滴鼻免疫小鼠,第28、35、42天再滴鼻接种rVVsyngp120或rVVmCN54gp120。体外测脾和肠系膜淋巴结(MLN)淋巴细胞增殖应答与CD8^ CTL应答。测血清和黏膜洗液特异的IgG和IgA,并测其是否中和实验室适应株HIV-1SF33。结果：单纯DNA免疫后,脾和MLN淋巴细胞在体外发生增殖应答和CTL应答,且测出血清特异的IgG和黏膜洗液特异的IgA。重组痘苗病毒末次免疫后第2周(第56天),发现rVVmCN54gp120增强MLN淋巴细胞增殖应答和CTL应答,脾CTL应答也增强。rVVsyngp120则增强MLN CTL应答。同时发现：2组重组痘苗病毒免疫的动物其血清中特异IgG抗体滴度均有所增高,但黏膜(粪便和阴道)洗液特异IgA抗体滴度却未增高,未测出血清特异IgA和黏膜洗液特异IgG。免疫血清可中和HIV-1SF33,而阴道洗液却不能。结论：单纯DNA疫苗滴鼻免疫可诱发较弱的系统和黏膜体液免疫与细胞免疫,但维持时间短。重组痘苗病毒主要增强局部黏膜的细胞免疫应答,且稍增强系统体液免疫应答,未增强黏膜的IgA应答。免疫血清有中和作用。

Systemic and local mucosal immune responses were induced by HIV-1CN54 DNA vaccine intranasally administered into mice and then boosted with recombinant Vaccina Virus

Objective To study whether recombinant Vaccina Virus syngp120 (rVVsyngp120) or mCN54gp120 (rVVmCN54gp120) candidate vaccine enhanced the immunogenity of syngp120 DNA vaccine intranasally administered into mice.Methods After DNA vaccine was administered into mice on 0, 7, 14, 21 d, rVVsyngp120 or rVVmCN54gp120 candidate vaccine was then intranasally administered into mice on 28, 35, 42 d. Detect spleen and MLN lymphocyte proliferation and CD8 +CTL response in vitro. Collection of serum and mucosal washes to detect antigen specific IgG and IgA antibody levels, and investigate whether it can neutralize HIV-1 SF33 strain.Results After single DNA immunization, spleen and MLN lymphocyte proliferation and CTL response were induced. Meanwhile, antigen specific IgG in serum and IgA in mucosal washes were also elicited.On 56 d, findings demonstrated that both MLN lymphocyte proliferation response and MLN and spleen CTL response were enhanced by rVVmCN54gp120. But MLN CTL response was enhanced by rVVsyngp120. Serum IgG antibody titer was weakly increased, but mucosal (including fecal and vaginal washes) IgA levels were not increased. Antigen specific IgA in serum or IgG in mucosal washes was hardly detected. It is serum but not vaginal washes can neutralize HIV-1 SF33.Conclusions Single DNA vaccine intranasally immunized induced weak systemic and mucosal immune responses (humoral and cellular), but kept in short time. rVVmCN54gp120 and rVVsyngp120 candidate vaccine mainly enhanced local mucosal cellular immune responses. Antigen specific IgG level in serum was weakly increased,while antigen specific IgA level in mucosal washes were not improved.