Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys

Barouch DH; Alter G; Broge T; Linde C; Ackerman ME; Brown EP; Borducchi EN; Smith KM; Nkolola JP; Liu JY; Shields J; Parenteau L; Whitney JB; Abbink P; Ng'ang'a DM; Seaman MS; Lavine CL; Perry JR; Li WJ; Colantonio AD; Lewis MG; Chen B; Wenschuh H; Reimer U; Piatak M; Lifson JD; Handley SA; Virgin HW; Koutsoukos M; Lorin C; Voss G; Weijtens M; Pau MG; Schuitemaker H

Science, Vol.349, No.6245, 320-324, 2015

DOI10.1126/science.aab3886 Export Citation

Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys

Barouch DH, Alter G, Broge T, Linde C, Ackerman ME, Brown EP, Borducchi EN, Smith KM, Nkolola JP, Liu JY, Shields J, Parenteau L, Whitney JB, Abbink P, Ng'ang'a DM, Seaman MS, Lavine CL, Perry JR, Li WJ, Colantonio AD, Lewis MG, Chen B, Wenschuh H, Reimer U, Piatak M, Lifson JD, Handley SA, Virgin HW, Koutsoukos M, Lorin C, Voss G, Weijtens M, Pau MG, Schuitemaker H

Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repeated, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repeated, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys.