Formalin inactivated junin virus: Immunogenicity and protection assays

Abstract

The aim of this study was to determine if Junin virus inactivated with formalin (FA) was immunogenic and able to elicit a protective response in the guinea pig. The XJ-Clone 3 strain of Junin virus grown in Vero cells was exposed to FA at 0 degrees C. The following inactivated antigens were prepared: A1, 0.1% FA for 50 hr; A2, 0.1% FA for 50 hr followed by concentration with polyethylene glycol (PEG); B1, 0.05% FA for 70 hr; B2, 0.05% FA for 70 hr plus PEG concentration; C, 0.1% FA for 50 hr followed by ultracentrifugation and purification by sucrose gradient. No residual infectivity was detected in any inactivated antigen either after two passages in newborn mice or by coculture with Vero cells. After immunization, high-neutralizing and low-immunofluorescent antibody titers wer obtained in adult mice and guinea pigs, thus showing that antigenicity was preserved. However, in spite of the presence of neutralizing antibodies, guinea pigs gained no protection against challenge with the highly pathogenic XJ strain. These results suggest that antibody amount and/or quality may be inadequate; alternatively, mechanisms other than humoral immunity, such as cellular response, not elicited by inactivated antigens may be essential for protection against Junin virus.

Junín Virus Pathogenesis and Virus Replication

“…The XJCl3 strain of JUNV grown in Vero cells was subjected to formalin inactivation at 0°C followed by concentration with polyethylene glycol (PEG). Immunization of guinea pigs with the prepared antigens resulted in the development of high neutralizing titers; however, no protection was gained against the following challenge with the with the highly pathogenic XJ strain [114]. These results suggested that alternative methods of antigen preparation and/or delivery may be required to elicit protective immunity.…”

Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection

“…This argued against infection-associated lymphoid depletion and immunosuppression as sole reasons for poor LASV nAb induction [ 19 , 20 ]. In contrast to LASV, passive serum therapy represents an efficient treatment against Argentine hemorrhagic fever [ 21 ] and formalin-inactivated JUNV, unlike LASV, can induce potent nAb responses [ 22 ]. The reasons underlying differential behavior of JUNV and LASV have remained unclear though.…”

The nucleoprotein of Pichinde virus expressed by a vaccinia-Pichinde virus recombinant partially protects hamsters from lethal virus challenge

“…Inactivated Lassa virus used in primates was able to induce antibodies against the nucteoprotein and glycoproteins, but not anti-Lassa cellular responses, and could not protect against Lassa infection [21]. Similarly inactivated XJ-clone 3 of Junin virus used as a vaccine in guinea pigs generated antibodies but was not protective [33], but priming guinea pigs or monkeys with live-attenuated Junin virus, produced protective immune responses [22,33]. Guinea pigs immunized with live vaccinia-Lassa virus recombinants had no detectable serum anti-Lassa antibody prior to challenge, but were protected [2,24].…”