Antibody-based vaccine for tuberculosis: validation in horse foals challenged with the TB-related pathogen Rhodococcus equi

Abstract

and ncohen@cvm.tamu.edu 17 oligosaccharides composed of only β-1→6-linked glucosamine conjugated to a carrier 86 protein such as tetanus toxoid (TT), (11, 23, 26, 27) complement-fixing, microbial-killing, 87 and protective antibody to PNAG can be induced. A final premise justifying evaluation 88 of vaccine-induced immunity to R. equi by immunizing pregnant mares is that foals are 89 considered to be infected soon after birth (28) when they are more susceptible to 90 infection (29) and when their immune system is less effective in responding to vaccines, 91 (30-33) which precludes active immunization of very young foals as a strategy for 92 vaccine evaluation against R. equi. 93 Therefore, in order to ascertain if R. equi pneumonia could be prevented by 94 antibody to PNAG, pregnant mares were vaccinated with the 5GlcNH 2 -TT vaccine, the 95 transfer of functional opsonic antibodies via colostrum to foals verified, and foals were 96 then challenged at 25-28 days of life with virulent R. equi. This approach protected 11 of 97 12 (92%) foals born to immunized mares against essentially all signs of clinical 98 pneumonia, whereas 6 of 7 (86%) foals born to non-immune, control mares developed 99 R. equi pneumonia. A follow-up study in which 2 liters (approximately 40 ml/kg) of 100 hyperimmune plasma from adult horses immunized with the 5GlcNH 2 -TT vaccine were 101 infused into newborn foals on day 1 of life similarly protected 5 of 5 (100%) of the 102 recipients from R. equi pneumonia following challenge at 4 weeks of life whereas 103 recipients of control plasma all developed clinical signs of pneumonia (4/4). In vitro 104 correlates of immunity were further investigated, and a novel mechanism of killing of 105 intracellular R. equi and other intracellular bacterial pathogens was identified, wherein 106 intracellular bacterial growth resulted in high levels of surface-expressed PNAG 107 intercalated into the plasma membrane of infected host cells, which served as a target

Precise protein conjugation technology for the construction of homogenous glycovaccines

“…12 The current candidate AV0328 consists of a pentamer (5GlcNH2:TT) and has been shown to elicit protective antibodies against Rhodococcus equi in horse foals. 13 The discussed approaches for the construction of synthetic glycoconjugate vaccines focus on the chemical synthesis of the carbohydrate antigen moiety, which allows better control relative to the use of antigen fragments. The conjugation strategies of these licenced or advanced vaccine candidates, however still relies on random conjugation towards reactive amino acid residues of the carrier protein.…”