RESULTS
Analysis of the demographic characteristics of the subjects in the two
SMV trials indicated no significant differences in sex, age, and
secretor status between subjects challenged with SMV Inoculum 1 and
Inoculum 2 (Table 2).
We compared infection and illness rates between the subjects who
received SMV Inoculum 1 (n=15) to those who received SMV Inoculum 2
(n=33). Overall, SMV infection occurred in 9 of 15 (60%) subjects
challenged with Inoculum 1 and in 25 of 33 (75.7%) subjects challenged
with Inoculum 2. Illness occurred in 7 of 15 (46.7%) subjects
challenged with Inoculum 1 and in 9 of 33 (27.3%) subjects challenged
with Inoculum 2. There were no statistically significant differences
between the infection (60.0% vs. 75.7%) and illness (46.7% vs.
27.3%) rates in the two trials (Table 3).
In addition to examining the infection and illness rates following SMV
challenge, we explored possible differences in severity of illness in
the 16 infected subjects who met our definition of illness (Table 4).
Subjects infected with SMV Inoculum 1 had a mean severity score of 6.00
(95% CI: 4.97, 7.03], whereas the mean severity score for subjects
infected with SMV inoculum 2 was significantly lower 2.94 (95% CI:
1.74, 4.14, P = 0.003) (Table 4, Figure 1). Furthermore, our analysis
indicates that Inoculum 1 was associated with more severe acute
gastroenteritis even at doses more than 100-fold lower than the doses
used for the Inoculum 2 challenge. In addition, we found
secretor-positive subjects had significantly higher mean modified
Vesikari severity scores compared to secretor-negative subjects (P
< 0.001) at the dose of 1.2×107 genome
copies (Figure 1). When we combined all data from both inocula and
different challenge doses, we did not find a significant association
between log10 inoculum dose and modified Vesikari scores
for either inoculum (Inoculum 1 and 2, P = 0.951 and P = 0.905,
respectively).
The RT-PCR results (Table 5) indicated that the NV positive rate was not
significantly different in subjects infected with Inoculum 1 vs.
inoculum 2 in stool samples collected during the first three days post
challenge, but subjects infected with Inoculum 1 had significantly more
(P < 0.001) PCR-positive stools during days 4-6 post challenge
(46.6%) compared to none of the subjects infected with Inoculum 2
having PCR-positive stool samples during that period of time. When
shedding duration was compared between these two groups, SMV RNA was
detected in three stool samples (9.1%) from days 15-45 post-challenge
from subjects challenged with Inoculum 2, but no subject challenged with
Inoculum 1 shed virus at 15 and 45 days post-challenge.
Finally, we compared anti-SMV serum IgG conversion (>4-fold
vs. pre-challenge) in subjects challenged with Inoculum 1 and Inoculum 2
(Table 5). During days 1 - 3 post challenge, none of subjects in both
groups showed anti-SMV serum IgG conversion. During days 4 - 6
post-challenge, eight subjects (57.1%) infected with Inoculum 1 showed
anti-SMV serum IgG conversion compared to none of the subjects infected
with Inoculum 2 (P < 0.001) during that period. Most serum IgG
conversion occurred between 15 and 30 days post challenge, but there was
no significant difference between the two trials in the overall
proportion of subjects with seroconversion.