Combinations of 3-hydroxyphthalic anhydride-modified ovalbumin with antiretroviral drug-based microbicide candidates display synergistic and complementary effects against HIV-1 infection.
BACKGROUND
The development of a safe, effective, and affordable microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a broad spectrum of HIV, simian immunodeficiency virus, and herpes simplex virus, making it a promising candidate as a component of combination microbicide. We intended to evaluate potential the synergistic anti-HIV-1 effect of HP-OVA in combination with antiretroviral drug (ARV)-based microbicide candidates.


METHODS
The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100, and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781, and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by enzyme-linked immunosorbent assay.


RESULTS
When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and -resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least 1 month and only induced weak immune responses after its multiple applications in the vaginas of rats.


CONCLUSIONS
Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses.
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Lin
L
Li
Suiyi
S
Tan
Hong
H
Lu
Lu
L
Lu
Jie
J
Yang
Hong
H
Jin
Shuwen
S
Liu
Shibo
S
Jiang
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002645:Chickens; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D010047:Ovalbumin / Q000737:chemistry / Q000627:therapeutic use*; D010796:Phthalic Anhydrides / Q000737:chemistry*; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D023581:HIV Fusion Inhibitors; D010796:Phthalic Anhydrides; D018894:Reverse Transcriptase Inhibitors; C478070:3-hydroxyphthalic anhydride; D010047:Ovalbumin
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