Evaluation of five temperature-sensitive mutants of respiratory syncytial virus in primates: I. Viral shedding, immunologic response, and associated illness

✍ Scribed by Dr. Linda S. Richardson; Robert B. Belshe; William T. London; D. Lewis Sly; David A. Prevar; Ena Camargo; Robert M. Chanock

• Publisher: John Wiley and Sons
• Year: 1978
• Tongue: English
• Weight: 564 KB
• Volume: 3
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.1890030202

✦ Synopsis

Abstract

Approximately 10^4^ plaque‐forming units (pfu) of five temperature‐sensitive (ts) mutants of respiratory syncytial (RS) virus were administered intranasally to seronegative chimpanzees to evaluate their level of attenuation. When the ts‐1 mutant was given to two chimpanzees, the pattern of viral growth and illness (rhinorrhea) was similar to that seen during wild‐type RS virus infection. Two further defective subclones of ts‐1, ts‐1 NG‐1 and ts‐1 NG‐16, appeared more attenuated than ts‐1 with respect to severity of rhinorrhea. The ts‐7 mutant infected the one animal tested; illness was similar to that induced by ts‐1 or wild‐type virus. 10^4^ pfu of the ts‐2 mutant failed to infect two chimpanzees; virus was not isolated, a serum antibody response was not detected, and unlike chimpanzees given the other ts mutants, these animals were not resistant to challenge with wild‐type virus. A 40‐fold larger inoculum of ts‐2, 10^5, 6^pfu, infected each of four chimpanzees, but the peak quantity of virus shed was approximately 500‐fold lower than during wild‐type virus infection. Significantly, the ts‐2 infected chimpanzees did not become ill, but infection did stimulate the development of RS virus serum neutralizing antibodies. The one chimpanzee given 10^7, 6^ pfu of the ts‐2 mutant shed as much virus as the chimpanzees infected with wild‐type virus; however, there were no signs of upper respiratory tract illness. Owl monkeys resembled chimpanzees in shedding s large amount of virus and developing rhinorrhea following administration of wild‐type virus or the ts‐1 mutant. Significantly, 10^5, 3^ pfu of ts‐2 infected only one of two owl monkeys tested, but a small quantity of virus (>10 pfu/ml) was shed. These observations suggested that the ts‐2 mutant was the most attenuated vaccine cadidate strain tested, and that extent of infection with rs‐2 appeared to be related to the quantity of virus administered.