Immunogenicity, safety, and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys

Abstract

An inactivated vaccine for severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was evaluated in rhesus monkeys. The monkeys were inoculated intramuscularly (i.m.) with 0.5, 5, 50, or 5000 microg of vaccine, or PBS as control, and boosted on day 7. After 3 weeks, they were challenged with the NS-1 strain of SARS-CoV. The humoral and mucosal immune responses, clinical signs, chemical indices and viremia were monitored following the immunization and challenge. The control animals who received PBS developed atypical SAR-CoV infection after viral challenge, according to clinical, virological and pathological findings. No systematic side effects were observed in vaccinated animals post-immunization, even in at the high dose of 5000 microg. The 50 microg dosage of vaccine elicited SARS-CoV specific immune responses against viral infection as compared to the partial immunity elicited by 0.5 and 5 microg doses. The results show that this inactivated vaccine can induce effective concomitant humoral and mucosal immunity against SARS-CoV infection, is safe in monkeys, and the vaccine maybe a good candidate for clinical trials.

Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques

“…This result, coupled with our findings, may provide an impetus for the reporting of macaque origins in pathogenesis studies and spur research into the functional consequences of these regional differences. Currently, macaque origins are rarely specified in methods sections of immunology and pathogenesis publications (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54), though this data may be profoundly influential.…”

The Immunobiology of SARS

“…Other vaccine strategies including DNA vaccine (162)(163)(164), inactivated whole virus vaccine (142,(165)(166)(167), and recombinant protein vaccine (168,169) were also immunogenic and efficacious in animal models. Many investigators have optimized the codon usage of the gene target to improve expression.…”

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

“…It is now known that the virus replication in nasal and lung tissues occurs at a much higher level than previously appreciated and is poorly represented by shed virus (24). Also, in two of the above-mentioned studies (6,7), protective efficacy of SARS-CoV vaccine candidates was evaluated by analysis of lung tissues collected by biopsy or necropsy on days 12 or 15 after the challenge; however, the virus is normally cleared by this time (24). Thus, evaluation of vaccine efficacy necessitates direct quantitative virological analysis of infected tissues at the peak of viral replication.…”

“…Inactivated whole-virus preparations of SARS-CoV have been shown to induce protective immunity in small-animal models (2)(3)(4)(5) and primates (6,7). However, large-scale growth of a highly pathogenic agent introduces the risk of laboratory infection, which indeed has occurred (8).…”

“…An additional limitation of previous studies of vectored and inactivated SARS-CoV vaccines in non-human primates, the model that is most similar to humans, is that protective efficacy was measured by quantitation of challenge SARS-CoV shed in respiratory secretions (6,7,16,20). It is now known that the virus replication in nasal and lung tissues occurs at a much higher level than previously appreciated and is poorly represented by shed virus (24).…”