In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 12 ( 2020-06-15), p. 3315-3328
Abstract:
Because of microbicide noncompliance and lack of a durable, highly effective vaccine, a combined approach might improve HIV prophylaxis. We tested whether a vaccine–microbicide combination would enhance protection against SIV infection in rhesus macaques. Four macaque groups included vaccine only, vaccine–microbicide, microbicide only, and controls. Vaccine groups were primed twice mucosally with replicating adenovirus type 5 host range mutant SIV env/rev, gag, and nef recombinants and boosted twice i.m. with SIV gp120 proteins in alum. Controls and the microbicide-only group received adenovirus type 5 host range mutant empty vector and alum. The microbicide was SAMT-247, a 2-mercaptobenzamide thioester that targets the viral nucleocapsid protein NCp7, causing zinc ejection and preventing RNA encapsidation. Following vaccination, macaques were challenged intravaginally with repeated weekly low doses of SIVmac251 administered 3 h after application of 0.8% SAMT-247 gel (vaccine–microbicide and microbicide groups) or placebo gel (vaccine-only and control groups). The microbicide-only group exhibited potent protection; 10 of 12 macaques remained uninfected following 15 SIV challenges. The vaccine-only group developed strong mucosal and systemic humoral and cellular immunity but did not exhibit delayed acquisition compared with adjuvant controls. However, the vaccine–microbicide group exhibited significant acquisition delay compared with both control and vaccine-only groups, indicating further exploration of the combination strategy is warranted. Impaired protection in the vaccine–microbicide group compared with the microbicide-only group was not attributed to a vaccine-induced increase in SIV target cells. Possible Ab-dependent enhancement will be further investigated. The potent protection provided by SAMT-247 encourages its movement into human clinical trials.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.2000165
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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