无针设备和含CpG佐剂的DNA可改善DNA疫苗以及改良痘苗病毒安卡拉载体候选疫苗的抗HIV抗体反应。

Needle-Free Devices and CpG-Adjuvanted DNA Improve Anti-HIV Antibody Responses of Both DNA and Modified Vaccinia Ankara-Vectored Candidate Vaccines.

作者信息

Chapman Rosamund, van Diepen Michiel, Douglass Nicola, Hermanus Tandile, Moore Penny L, Williamson Anna-Lise

机构信息

Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa.

Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa.

出版信息

Vaccines (Basel). 2023 Feb 7;11(2):376. doi: 10.3390/vaccines11020376.

DOI:10.3390/vaccines11020376

PMID:36851255

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9965773/

Abstract

The combination of mosaic Gag and CAP256 envelope in an HIV vaccine regimen comprising DNA prime and modified vaccinia Ankara (MVA) boost followed by protein boost has previously been shown to generate robust autologous Tier 2 neutralizing antibodies (nAbs) in rabbits. Further refinements of this strategy have been investigated to improve antibody responses. The delivery of both DNA and recombinant MVA vaccines with a needle-free device was compared to delivery by injection, and the effect of formulating the DNA vaccine with adjuvant CpG ODN 1826 was determined. The Pharmajet Stratis needle-free injection device (PharmaJet, Golden, CO, USA) improved binding antibody responses to the DNA vaccine as well as both binding and neutralizing antibody responses to the MVA vaccines. Formulation of the DNA vaccines with CpG adjuvant further improved the antibody responses. A shortened vaccination regimen of a single DNA inoculation followed by a single MVA inoculation did not elicit Tier 1B nor Tier 2 neutralization responses as produced by the two DNA, followed by two MVA vaccination regimen. This study showed the immunogenicity of HIV DNA and MVA vaccines administered in a DDMM regimen could be improved using the PharmaJet Stratis needle-free injection device and formulation of the DNA vaccines with CpG adjuvant.

摘要

在一种包含DNA初免、改良痘苗病毒安卡拉（MVA）加强免疫随后进行蛋白加强免疫的HIV疫苗方案中，镶嵌型Gag和CAP256包膜的组合此前已被证明能在兔子体内产生强大的自体2级中和抗体（nAbs）。为了改善抗体反应，人们对该策略进行了进一步优化。将使用无针装置递送DNA和重组MVA疫苗与注射递送进行了比较，并确定了用佐剂CpG ODN 1826配制DNA疫苗的效果。Pharmajet Stratis无针注射装置（美国科罗拉多州戈尔登市的Pharmajet公司）改善了对DNA疫苗的结合抗体反应以及对MVA疫苗的结合和中和抗体反应。用CpG佐剂配制DNA疫苗进一步改善了抗体反应。与两次DNA接种后再进行两次MVA接种方案所产生的1B级和2级中和反应不同，单次DNA接种后再进行单次MVA接种的缩短疫苗接种方案未引发此类反应。这项研究表明，使用Pharmajet Stratis无针注射装置和用CpG佐剂配制DNA疫苗，可以提高以DDMM方案接种的HIV DNA和MVA疫苗的免疫原性。