Influenza Infection in the Infant Mouse

Abstract

SummaryA nonlethal influenza infection [A/PC/1/73 (H3Nz)l was given to infant mice to determine (1) the pathology of tracheal epithelium and lung, (2) the time course of viral shedding from the nose and lung, and (3) the subsequent development of protective immunity during adulthood.Both desquamation of the tracheal epithelium and lung pathology similar to that described in adults after influenza infection were observed in the infant. Animals infected at 3 days of age show virus shedding in 12 of 13 infant mice that persists for at least 2 days longer than in the adult. This longer duration of influenza infection did not result from either malnutrition or from intralitter transmission of virus. Recovery from virus shedding in both the upper and lower airway occurred in the absence of detectable serum antibody in six of seven mice. Infants that recover from infection, when rechallenged during adulthood, manifest complete protection in 11 of 13 mice after nonlethal challenge and no mortality after lethal challenge. Abbreviations EID50, egg infectious dose 50% MID50, mouse infectious dose 50% MLD5,, mouse lethal dose 50% NK, natural killer Influenza infection is responsible for producing significant morbidity and mortality in the human infant (4,14). The pathology of influenza disease in the adult mouse corresponds to influenza in human adults (22). This suggests that the young mouse might be a good model for studying factors responsible for the severity of influenza in the infant human. Although studies of lethal influenza infection of infant animals have been reported (3,5,12,19,23), the suitability of the infant mouse as a model for nonlethal influenza infection in the newborn has not been reported. We therefore undertook the present study to determine (1) the pathology of influenza infection, (2) recovery from influenza virus shedding, and (3) the development of subsequent protective immunity against influenza in the infant mouse. MATERIALS AND METHODS Animals.Eight to ten-week-old, inbred Swiss white mice of the A/J strain were obtained from Jackson Laboratories, Bar Harbor, ME. These animals were housed and bred in the animal facilities of the College of Medicine, University of Florida. All experimental and control mice were housed in the same environment and treated similarly.Breeding. Eight female mice were housed per cage and separated from male mice for at least 1 wk before breeding. At the time of mating no more than two female mice were placed in each cage containing one male. Males were removed at the end of 4 days. Two weeks later, pregnant females were isolated in individual cages. Approximately 20% of mothers would deliver on each of 2 days, 21 days after the 4-day breeding period.Virus. A/Port Chalmers/l/73 (A/PC/1/73 H3N2) influenza virus was originally obtained from the Research Resources Branch, National Institutes of Allergy and Infectious Disease. This was passaged multiple times in eggs to provide a large stock of virus that contained EID50/ml. This virus was also passaged six times in mouse ...

A single immunization with inactivated H1N1 influenza vaccine formulated with delta inulin adjuvant (Advax™) overcomes pregnancy-associated immune suppression and enhances passive neonatal protection

“…It has previously been demonstrated that acquisition of influenza-specific antibody in neonatal mice is predominantly mediated by breast-feeding [23]. We hypothesized that enhanced protection of pups of dams receiving iPR8+Advax could likewise be due to enhanced breast milk transfer of maternal IgG.…”

“…Maternal antibody acquired by pups through transplacental transfer or breast milk provides a critical mechanism of protection against infection during the period of neonatal immune immaturity [22, 23]. We wished, therefore, to see whether the addition of Advax adjuvant to vaccine administered to pregnant mothers could enhance protection of their unimmunized pups.…”

Nonhuman primate infants have an impaired respiratory but not systemic IgG antibody response following influenza virus infection

“…In a mouse model using 3 day old animals, 1 of 5 animals exhibited positive antibody titers at 13 days postinfection compared to 5 of 5 adults [36]. The vast majority of additional data available in relation to influenza-specific immune responses in infants is derived from studies of vaccination in humans.…”

Different virulence of influenza A virus strains and susceptibility to pneumococcal otitis media in chinchillas

“…Virus shedding persisted on day 7 in 2 of 10, 3 of 11, and 3 of 9 animals infected with the H3N2, HlNl, and CR29 strains, respectively. Likewise, in infant and adult mice infected with another H3N2 strain (A/PC/l/73), peak nasal wash virus titers were 103.5 50% egg infective doses and virus shedding ceased before day 11 (29). Although virus titers from nasal turbunate homogenates were higher in infant rats infected with the H3N2, HIN1, and CR29 strains (3), Reuman et al found that virus titers were significantly lower in nasal homogenates than in nasal washes performed on the same animals (29).…”