A Lassa vaccine in primates with AIDS Lassa fever virus is a rodent-borne scourge in West Africa and, less has been classified as a Category A biothreat in the US because of its lethality and aerosol-transmissibility. Efforts to control Lassa fever focus largely on vaccine development, because the disease course is exceptionally rapid and effective therapies are usually too late. We developed a candidate attenuated vaccine, MOP/LAS that is a reassortant between Lassa Josiah strain and the avirulent Mopeia strain. It is an attenuated, infectious vaccine that protects guinea pigs from lethal challenge with Lassa fever virus. As part of our vaccine development plan, we want to understand the interactions between this Lassa fever vaccine and HIV, since these pathogens are endemic in the same regions of sub-Saharan Africa. In this study, we employ the SIV/macaque model for AIDS to simulate the immune-suppressed state of persons living with HIV. Our goal is to determine whether an attenuated arenavirus vaccine could be safe and immunogenic in macaques with SIV disease. These studies will touch on a broader issue that arose recently when 3 organ transplant recipients died due to LCMV infection of the transplanted tissue, thus raising the possibility that an ordinarily benign arenavirus can become virulent in immune-suppressed hosts. Our hypothesis is that an attenuated vaccine strain will not become more virulent in an AIDS- immunosupressed host. We propose to test this hypothesis in SIV-infected monkeys remaining from completed AIDS studies, and we will use criteria for virulent and benign arenavirus infections developed in our previous macaque studies.
Our specific aims are to: 1) Test the hypothesis that an attenuated Lassa vaccine (MOP/LAS) will remain attenuated in macaques where immunity is suppressed during SIV-acquired immunodeficiency syndrome (AIDS). 2) Test the hypothesis that AIDS monkeys given an attenuated arenavirus will develop robust immune responses to vaccine antigens. Our long-term goal is to deliver a vaccine against Lassa fever to West Africa, and to derive from these studies basic information on immune responses to vaccination in the context of AIDS. A successful Lassa fever vaccine should be safe and available to persons with HIV, and Lassa vaccination programs must anticipate any effect of endemic HIV on vaccine performance.
A Lassa vaccine in primates with AIDS Lassa fever virus causes a deadly disease in man and is a serious public health threat in West Africa. Though it can potentially be used in biowarfare, this family of viruses are not a serious health threat in the US (except for the rare incidence of lethal contamination for transplant patients). We developed a vaccine that successfully protected guinea pigs. We have the chance to test the vaccine in monkeys left over from an AIDS experiment, and this test will address the safety of our vaccines in people with AIDS. This is an important question since the Lassa endemic region of West Africa also has a high incidence of AIDS.
| Zapata, Juan C; Salvato, Maria S (2015) Genomic profiling of host responses to Lassa virus: therapeutic potential from primate to man. Future Virol 10:233-256 |
| Zapata, Juan C; Goicochea, Marco; Nadai, Yuka et al. (2014) Genetic variation in vitro and in vivo of an attenuated Lassa vaccine candidate. J Virol 88:3058-66 |
| Zapata, Juan C; Poonia, Bhawna; Bryant, Joseph et al. (2013) An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity. Virol J 10:52 |
| Zapata, Juan C; Pauza, C David; Djavani, Mahmoud M et al. (2011) Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever. Antiviral Res 92:125-38 |
