Clues to finding correlates of risk/protection for HIV-1 vaccines

Abstract

Based on outcomes of informative HIV-1 vaccine prevention trials and the literature, it seems protection against HIV-1 acquisition more likely pertains to innate rather than adaptive immunity mechanisms. The proposed innate mechanism appears to be launched by alternatively activated macrophages in response to viral vectors and might be enhanced by natural female hormones.

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

“…We were first to suggest HERV-K102 is a replication competent live virus both in vitro and in vivo [10,67] and provided evidence that its replication may protect against HIV-1 acquisition ie., generates sterilizing immunity [10,67]. Other virologists have also unwittingly isolated HERV-K HML-2 DNA containing particles at the same low levels and frequencies from HIV-1 infected patients [68] in direct support of our findings as discussed elsewhere [11]. The goals of the present paper is to ask what host innate immunity mechanisms are abrogated by ADE infection into macrophages and why does this cause and determine progression to more severe disease.…”

“…Given the importance of ADE as an impediment to the development of safe and effective vaccines against emerging and pandemic viruses including SARS-CoV-2, it is important to understand what is so special about the M1-like, proinflammatory foamy macrophages and to elucidate how they generate a potent virus-anti-virus (heterologous) response. Human endogenous retrovirus K102 (HERV-K102) replication produces particles in M1-like macrophages and generates a foamy appearance when the particles bud into vacuoles (Figure 4) [10,11,67]. We were first to suggest HERV-K102 is a replication competent live virus both in vitro and in vivo [10,67] and provided evidence that its replication may protect against HIV-1 acquisition ie., generates sterilizing immunity [10,67].…”

“…Answers to these questions are relevant to allcause mortality and thus human survival and so, are needed for preparation for future pandemics. [10,11,67]. Left image: H&E staining of a CB sample (cytospin slide) showing the dominant presence of highly vacuolated foamy macrophages amongst normal small lymphocytes (400X).…”

“…Reproduced from "Clues to finding correlates of risk/protection for HIV-1 vaccines", by Laderoute MP. 2018;6:868 [11]. CC BY Author.…”

“…It should be appreciated that hypoxia and inflammasome activation results in foam cell formation in M1-like proinflammatory macrophages [9]. Accordingly, it appears, pro-inflammatory foamy macrophages provide protection against HIV-1 acquisition, a conclusion reached earlier on entirely different evidence [10,11].…”