Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.
Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02.
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DOI：
10.1371/journal.pone.0037220
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ogasawara K
中科院分区：
文献类型：
--
作者：
Arikata M;Itoh Y;Okamatsu M;Maeda T;Shiina T;Tanaka K;Suzuki S;Nakayama M;Sakoda Y;Ishigaki H;Takada A;Ishida H;Soda K;Pham VL;Tsuchiya H;Nakamura S;Torii R;Shimizu T;Inoko H;Ohkubo I;Kida H;Ogasawara K
我们从由144个（= 16 HA×9 NA）非致病性甲型流感病毒组成的病毒库中制备了H1N1候选疫苗，并使用免疫学幼稚的食蟹猴检查了其对大流行（2009）H1N1毒株的保护作用，以排除预先存在的免疫力，并进行临床前研究，因为先前接种或感染流感病毒的人中预先存在的免疫力可能难以比较疫苗有效性。 此外，使用携带主要组织相容性复合物I类分子Mafa-A1*052∶02的猕猴来分析肽特异性CD 8 + T细胞应答。用未添加佐剂的灭活全颗粒制剂免疫的猕猴血清显示出比用裂解制剂免疫的猕猴血清更高的针对疫苗株A/北海道/2/1981（H1N1）的中和滴度。用裂解疫苗免疫两次的猕猴血清中针对大流行毒株A/Narita/1/2009（H1N1）的中和活性达到与用全颗粒疫苗免疫一次的猕猴血清中的中和活性相似的水平。接种大流行病毒后，未接种疫苗的猕猴感染后6天鼻标本中均检出病毒，接种全颗粒疫苗和裂解疫苗的猕猴感染后平均分别为2.67天和5.33天。在攻击感染后，在接种全颗粒疫苗的猕猴中观察到针对大流行病毒的回忆中和抗体应答和对与Mafa-A1 *052∶02结合的核蛋白肽NP 262 -270特异性的CD 8 + T细胞应答比接种裂解疫苗的猕猴中观察到的应答更迅速或更强烈。这些发现表明，从我们的病毒库中获得的疫苗对猕猴中的大流行性病毒感染是有效的，并且与裂解疫苗相比，全颗粒疫苗赋予猕猴针对大流行性流感病毒感染的更有效的记忆和更广泛的交叉反应性免疫应答。
We made an H1N1 vaccine candidate from a virus library consisting of 144 ( = 16 HA×9 NA) non-pathogenic influenza A viruses and examined its protective effects against a pandemic (2009) H1N1 strain using immunologically naïve cynomolgus macaques to exclude preexisting immunity and to employ a preclinical study since preexisting immunity in humans previously vaccinated or infected with influenza virus might make comparison of vaccine efficacy difficult. Furthermore, macaques carrying a major histocompatibility complex class I molecule, Mafa-A1*052∶02, were used to analyze peptide-specific CD8+ T cell responses. Sera of macaques immunized with an inactivated whole particle formulation without addition of an adjuvant showed higher neutralization titers against the vaccine strain A/Hokkaido/2/1981 (H1N1) than did sera of macaques immunized with a split formulation. Neutralization activities against the pandemic strain A/Narita/1/2009 (H1N1) in sera of macaques immunized twice with the split vaccine reached levels similar to those in sera of macaques immunized once with the whole particle vaccine. After inoculation with the pandemic virus, the virus was detected in nasal samples of unvaccinated macaques for 6 days after infection and for 2.67 days and 5.33 days on average in macaques vaccinated with the whole particle vaccine and the split vaccine, respectively. After the challenge infection, recall neutralizing antibody responses against the pandemic virus and CD8+ T cell responses specific for nucleoprotein peptide NP262-270 bound to Mafa-A1*052∶02 in macaques vaccinated with the whole particle vaccine were observed more promptly or more vigorously than those in macaques vaccinated with the split vaccine. These findings demonstrated that the vaccine derived from our virus library was effective for pandemic virus infection in macaques and that the whole particle vaccine conferred more effective memory and broader cross-reactive immune responses to macaques against pandemic influenza virus infection than did the split vaccine.
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