A combination HIV vaccine based on Tat and Env proteins was immunogenic and protected macaques from mucosal SHIV challenge in a pilot study

作者：Ferrantelli Flavia; Maggiorella Maria Teresa; Schiavoni Ilaria; Sernicola Leonardo; Olivieri Erika; Farcomeni Stefania; Pavone Cossut Maria Rosaria; Moretti Sonia; Belli Roberto; Collacchi Barbara; Srivastava Indresh K; Titti Fausto; Cafaro Aurelio; Barnett Susan W; Ensoli Barbara^*

来源：Vaccine, 2011, 29(16): 2918-2932.

DOI：10.1016/j.vaccine.2011.02.006

• HIV/AIDS vaccine
• Neutralizing antibodies
• Mucosal R5 SHIV challenge

HIV native Tat and V2 loop-deleted Env (Env Delta V2) proteins already proved safe and immunogenic in phase I clinical testing as single vaccine components. Further, a phase II vaccine trial with Tat showed intensification of the therapeutic effects of HAART in successfully treated HIV-infected individuals. Here a pilot study assessed the immunogenicity and protective efficacy of an HIV/AIDS vaccine based on the combination of Tat and Env Delta V2 proteins in cynomolgus macaques against homologous intrarectal challenge with 35 MID(50) (monkey infectious dose 50) of an R5 simian-human immunodeficiency virus (SHIV(SF162P4cy)).
Upon challenge, three of four macaques immunized with Tat and Env Delta V2, and two of three monkeys immunized with Env Delta V2 alone were protected from infection. In contrast, all three control animals, which had been either administered with the adjuvants only or left untreated, and an additional monkey immunized with Tat alone became systemically infected. Protection of the macaques vaccinated with Env Delta V2 or Tat/Env Delta V2 correlated with higher peak titers of pre-challenge neutralizing antibodies obtained during the immunization period (between 70 and 3 weeks before challenge) and with anti-Env V3 loop binding antibodies assessed 3 weeks before challenge.
Compared to Env Delta V2 alone, the Tat and Env Delta V2 combined vaccine elicited faster antibody responses (IgM) with a trend, early in the vaccination schedule, after the second immunization including Env Delta V2, towards broader anti-Env IgG epitope specificity and a higher ratio of neutralizing to Env-binding antibody titers. As the number of immunizations increased, vaccination with Env Delta V2 approached the immune response assessed after two inocula with the Tat/Env Delta V2 combined vaccine, even though some differences remained between groups, as indicated by anti-Env IgG epitope mapping. In fact, three weeks before challenge, plasma IgG of animals in the Env Delta V2 group showed a trend towards stronger specificity for the V1 loop and V5 loop-C5 regions of Env, whereas the Tat/Env Delta V2 group displayed an overall higher reactivity for epitopes within the Env V3 loop throughout the immunization period.
Although differences in terms of protection rate were not found between the Env Delta V2 or Tat/Env Delta V2 vaccination groups in this pilot study, vaccination with Tat/Env Delta V2 appeared to accelerate the induction of potentially protective antibody responses to Env. In particular, antibodies to the Env V3 loop, whose levels at pre-challenge correlated with protection, were already higher early in the vaccination schedule in monkeys immunized with Tat/Env Delta V2 as compared to Env Delta V2 alone.
Further studies including larger vaccination groups and fewer immunizations with these two vaccine candidates are needed to confirm these findings and to assess whether the Tat/Env Delta V2 vaccine may afford superior protection against infection.

• 出版日期2011-4-5