Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine.

Bikash Sahay,Janet Yamamoto

doi:10.3390/v10050277

Abstract

The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax® FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A–E). This vaccine consists of inactivated dual-subtype (A plus D) FIV-infected cells, whereas its prototype vaccine consists of inactivated dual-subtype whole viruses. Both vaccines in experimental trials conferred moderate-to-substantial protection against heterologous strains from homologous and heterologous subtypes. Importantly, a recent case-control field study of Fel-O-Vax-vaccinated cats with outdoor access and ≥3 years of annual vaccine boost, resulted in a vaccine efficacy of 56% in Australia where subtype-A viruses prevail. Remarkably, this protection rate is far better than the protection rate of 31.2% observed in the best HIV-1 vaccine (RV144) trial. Current review describes the findings from the commercial and prototype vaccine trials and compares their immune correlates of protection. The studies described in this review demonstrate the overarching importance of ant-FIV T-cell immunity more than anti-FIV antibody immunity in affording protection. Thus, future efforts in developing the next generation FIV vaccine and the first effective HIV-1 vaccine should consider incorporating highly conserved protective T-cell epitopes together with the conserved protective B-cell epitopes, but without inducing adverse factors that eliminate efficacy.

Highlights

Feline immunodeficiency virus (FIV) was discovered in the fall of 1986 from a stray cat cattery in northern California [1]
The commercial vaccine carries a higher concentration of surface envelope glycoproteins (SU Env, gp100) and/or the varying configurations of SU Env expression compared to the prototype vaccine
neutralizing antibody (NAb) conferred significant protection against homologous FIVPet but conferred no protection against heterologous FIVFC1 (Table 4). These findings suggested that protection against vaccine virus FIVPet was mainly mediated by antibody immunity including NAbs

Summary

Introduction

Feline immunodeficiency virus (FIV) was discovered in the fall of 1986 from a stray cat cattery in northern California [1]. The infected CD4+ T cells die of apoptosis causing the CD4/CD8 T-cell inversion, the hallmark of all three AIDS-causing lentiviruses (HIV-1, FIV, and SIV) [4,10,11,12]. Components of the Commercial and Prototype FIV Vaccines. Both Fel-O-Vax® and its prototype FIV vaccines contain inactivated two subtypes, FIVPet (subtype A). The commercial vaccine is composed of inactivated FIVPet -infected whole cells (FIVPet -IWC) and FIVShi -IWC in FD-1 adjuvant (2 × 107 cells total with about 50 μg of total viruses in the fluid). The prototype vaccine comprises of paraformaldehyde-inactivated pelleted whole viruses (IWV) (250 μg of each virus) in the same adjuvant supplemented with either human or feline IL-12 to enhance anti-FIV T-cell immunity.

Methods

Findings

Conclusion