Neutralization-resistant virus challenges the way to protect against HIV
Reports on neutralization-sensitive virus challenges working well in animal models still progress timidly towards human studies due to human efficacy trials that report low protective response of vaccine candidates predicted by animal studies. This is driving the advent of a new genre of viral vaccines, the neutralization-resistant virus challenges towards the development of HIV and SIV vaccine.
Prime-boost strategy to create stronger immune responses
Viral vector vaccines generally consists of a live attenuated virus that is genetically engineered to carry DNA encoding protein antigens that can be tailored to stimulate a range of immune responses. Viral vectors are being used in combination with other vaccine technologies in a strategy called heterologous prime-boost. In this system, one vaccine is given as a priming step, followed by vaccination using an alternative vaccine or adjuvant as a booster. The heterologous prime-boost strategy provides a stronger overall immune response. Viral vector vaccines are being pursued as both prime and boost vaccines as part of this strategy.
Rhesus monkeys were primed with adenovirus serotype 26(Ad26) viral vectors (powered Johnson & Johnson’s Advac technology) at weeks 0 and 24 and subsequently boosted with purified envelope glycoprotein (AS01B-adjuvanted SIVmac251 Env gp140) at weeks 52, 56, and 60. Neutralization or binding-antibody responses were observed in all vaccinated animals and the antibody levels increased considerably at week 64 compared to week 28 when the adjuvant administration were also complete. This demonstrates the importance of the prime-boost methodology. Then these vaccinated animals were challenged with a series of repeated, heterologous SIVmac251, simian immunodeficiency virus similar to HIV that infects non-human primates. Although the 6 repeated doses lead to a 100 times severe infection than that seen in human, 50% of the injected animals showed complete protection. This study which is a collaboration between researchers at BIDMC, Harvard Medical School, Johnson & Johnson and several other institutes was published in Science and shows an effective and robust use of ‘prime-boost’ vaccines in non-human primates.
There is an ongoing phase I study to test the safety and immunogenicity of different components and a phase 1/2a study currently recruiting volunteers in the United States, Rwanda, South Africa, Thailand and Uganda. With no viral vector vaccines currently on market for use in humans, it would be interesting to observe with hope this vaccine’s journey through the ongoing clinical trials.