Janssen Vaccines & Prevention, Leiden, The Netherlands.
Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands.
Nat Commun. 2024 Apr 11;15(1):3128. doi: 10.1038/s41467-024-47492-1.
One of the strategies towards an effective HIV-1 vaccine is to elicit broadly neutralizing antibody responses that target the high HIV-1 Env diversity. Here, we present an HIV-1 vaccine candidate that consists of cobalt porphyrin-phospholipid (CoPoP) liposomes decorated with repaired and stabilized clade C HIV-1 Env trimers in a prefusion conformation. These particles exhibit high HIV-1 Env trimer decoration, serum stability and bind broadly neutralizing antibodies. Three sequential immunizations of female rabbits with CoPoP liposomes displaying a different clade C HIV-1 gp140 trimer at each dosing generate high HIV-1 Env-specific antibody responses. Additionally, serum neutralization is detectable against 18 of 20 multiclade tier 2 HIV-1 strains. Furthermore, the peak antibody titers induced by CoPoP liposomes can be recalled by subsequent heterologous immunization with Ad26-encoded membrane-bound stabilized Env antigens. Hence, a CoPoP liposome-based HIV-1 vaccine that can generate cross-clade neutralizing antibody immunity could potentially be a component of an efficacious HIV-1 vaccine.
一种有效的 HIV-1 疫苗策略是诱导针对高 HIV-1 Env 多样性的广泛中和抗体反应。在这里，我们提出了一种 HIV-1 疫苗候选物，它由钴卟啉磷脂（CoPoP）脂质体组成，这些脂质体用修复和稳定的 clade C HIV-1 Env 三聚体在预融合构象中进行了装饰。这些颗粒表现出高的 HIV-1 Env 三聚体装饰、血清稳定性和结合广泛中和抗体。用在每个剂量中显示不同 clade C HIV-1 gp140 三聚体的 CoPoP 脂质体对雌性兔子进行三次序贯免疫，可产生高的 HIV-1 Env 特异性抗体反应。此外，可检测到针对 20 种多 clade tier 2 HIV-1 株中的 18 种的血清中和作用。此外，CoPoP 脂质体诱导的峰值抗体滴度可通过随后用 Ad26 编码的膜结合稳定的 Env 抗原进行异源免疫来回忆。因此，基于 CoPoP 脂质体的 HIV-1 疫苗能够产生跨 clade 的中和抗体免疫，有可能成为有效 HIV-1 疫苗的一个组成部分。
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