Abstract: Human Immunodeficiency Virus (HIV) infected individuals produce broad multi-strain neutralising antibodies (bNAb) only after a long exposure to high viral loads. On the other hand, most HIV vaccines have not been successful at inducing bNAb. We previously showed that vaccination of a cow (7004) with HIV gp140 AD8 trimers resulted in a high titer of HIV Env specific IgG with strong bNAb activity in serum samples, and this polyclonal bNAb was concentrated into colostrum during pregnancy and calving. In this study we investigated the effect of extended HIV gp140 vaccination on bovine IgG activity from serum and colostrum samples for HIV Env binding and neutralisation.
Methods: Over a 4 year period (48.5 months) cow 7004 achieved 3 pregnancies and was vaccinated with 3 – 4 booster doses in each pregnancy. The regimen included booster vaccination at early and/or late intervals of pregnancy. Blood samples were collected at pre- and post-vaccination timepoints and the binding activity of each serum sample was analysed in Enzyme Linked Immunosorbent Assay (ELISA) against AD8 gp140 Env. The neutralising activity of 1/10 dilution of each serum sample and purified colostrum IgG was assessed using a pseudovirus reporter assay.
Results: A high HIV Env-specific IgG titer between 3.5 - 5 log10 was achieved in all serum and the end-point concentration for colostrum IgG samples was 3 log10 mg/ml. In addition, the neutralising activity of serum and colostrum IgG samples against MN pseudovirus was sustained for each sample through each pregnancy.
log10
Conclusion: Long-term vaccination resulted in a sustained high level of HIV specific antibody titer in serum and colostrum samples. In addition, the neutralisation activity against HIV reporter pseudovirus was retained, demonstrating the efficiency of the vaccine in eliciting clinically important antibodies.