Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara

Abstract

The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. Highlevel primary plasma viremia with subsequently increasing viremia was associated with rapid progression to AIDS (n ‫؍‬ 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associated with progression to AIDS within a year (n ‫؍‬ 6). Low levels of primary plasma viremia followed by sustained restriction of virus replication were associated with maintenance of normal lymphocyte subsets and intact lymphoid architecture (n ‫؍‬ 4), reminiscent of the profile observed in human immunodeficiency virus type 1-infected long-term nonprogressors. Three of four macaques that showed this pattern had been immunized with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and extent of virus replication to disease course and suggest that sustained suppression of virus promotes long-term, asymptomatic survival of SIV-infected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequent disease course, even if sterilizing immunity is not achieved.

On the analysis of viral load endpoints in HIV vaccine trials

“…In particular, baseline viral load shortly after acute infection (or 'viral load set point') has been shown to be highly prognostic for progression to AIDS [18][19][20] and is generally considered one of the best markers for disease progression in HIV seroconverters [21,22]. Similar results have been obtained in macaque challenge studies [23,24]; moreover, experimental interventions that reduced set point have been shown to delay disease progression [9,10,25]. Viral load has also been shown to be highly predictive of infectiousness [26] such that a vaccine's e ect on early viral load may also be a reasonable surrogate of VE I .…”

Utilizing poxviral vectored vaccines for antibody induction—Progress and prospects

“…Recombinant attenuated orthopoxviruses have also shown comparable immunogenicity to replication-competent vaccinia in numerous animal studies [38,[44][45][46]. Although most have focussed on T cell responses against the encoded transgenes, some have assessed antibody induction.…”

Critical Role of Perforin-dependent CD8+ T Cell Immunity for Rapid Protective Vaccination in a Murine Model for Human Smallpox

“…One promising VACV vaccine candidate is based on the highly attenuated virus strain modified VACV Ankara (MVA) [14][15][16]. MVA has also been developed as a nonreplicating viral vector to construct experimental recombinant vaccines against various infectious diseases [17][18][19][20][21][22]. Immunizations with MVA in animal models proved highly efficacious when compared to conventional VACV vaccines, and elicited antigenspecific humoral and cellular immune responses [19,[23][24][25][26][27][28][29][30].…”