Pediatr. Res. 14: 788-792 (1980)
gamma globulin
group B streptococcal immune globulin
group B streptococc
passive immuniza
tion
Protective Value of Gamma Globulin Preparations
against Group B Streptococcal Infections in Chick
Embryos and Mice
LAWRENCE C. VOGEL, ROBERTO R . KRETSCHMER. DONNA M . PADNOS. PE(;<;Y I>.
KELLY
A N D SAMUEL P. GOTOFF"'
Depurrrnent c$ Pediurrrc.\. Michael Reeye 1lo.vpiial and MedIcul ('enier. C'hrcc~~o.Illi,~or.s.US,.#
Summary
I'he protective value of pooled human gamma globulin (GG) and
a group B streptococcal immune globulin (GBSIG) was studied in
a chick embryo and a murine model of group B streptococcal
(GBS) infection. Chick embryos were protected by the I V administration of 0.4 to 0.8 mg of GG from three manufacturers against
I V challenge with type l a GBS. Two of three G G preparations at
doses of 0.4 to 1.65 mg protected chick embryos against type 111,
but 1.65 mg of all three preparations failed to protect against GBS
types I b and 11. Mice were protected from lethal I P challenges
with types l a and I b by the prior IM inoculation of three and two
of the three GG preparations at doses of 0.5 to 1.0 mg, respectively.
Administration IM of 1 mg of GG failed to protect mice against
types 11 and 111.
The I V administration of 0.2 mg of GBSIG protected chick
embryos against I V inoculation with GBS types la, Ib, 11, and 111.
Administration IM of 0.5 mg of GBSIG protected mice against I P
challenges with types la, Ib, and 11, but not with type 111. The I P
administration of 0.25 mg of G B S l C simultaneously with type 111
GBS protected mice, whereas GG was not protective. GBSIG
should undergo clinical trials for the prevention of GBS infections
and their recurrences and as a possible adjunct to antibiotic and
supportive therapy of severe GBS infections.
Speculation
Some human sera contain antibody which protects animals
against infection with group B streptococcus. I f passive immunization with human gamma globulin or group B streptococcal
immune globulin is effective i n animal models, i t may be potentially
useful i n preventing neonatal group B streptococcal infections,
and clinical trials would be indicated.
Group B streptococci (GBS) are major bacterial pathogens in
early infancy ( 1). Despite appropriate antimicrobial therapy, neonatal GBS infections are associated with a high morbidity and
mortality. suggesting that efforts be directed toward prevention of
these infections by active or passive immunoprophylaxis (9). One
predisposing factor in the development of neonatal GBS infections
is low concentrations of maternal transplacentally acquired, typespecific antibody (3, 4, 7, 21). Therefore. active immunization of
women of childbearing age would be an ideal approach in preventing neonatal GBS infections. Baker et al. (2) have described
a native type I11 carbohydrate antigen as a potential vaccine, and
preliminary studies in adult volunteers have shown that this
vaccine is immunogenic and safe.
Until vaccines for each of the five GBS types have been
developed and administered to the susceptible childbearing population. passive immunization might be used to prevent neonatal
GBS infections. Hyperimmune and pooled human gamma globulin ( G G ) have been used with variable success in the prophylaxis
and treatment of several viral and bacterial infections ( 17). Passi\
immunization of pregnant women or newborn infants m ~ g h tprc
vide protection to the infant during the first few months of life. 1
addition, passive immunization might be effective in preventin
recurrent GBS infections and may be a useful adjunct to antibiot
therapy.
Stewardson-Krieger er al. (15) have demonstrated that poole
G G at a dose as low as 0.3 ml/kg IM protected mice from lethi
IP challenges with type la GBS. These investigations have bee
extended to include G G from three different manufacturers an
passive protection studies in both mice and chick embryos usin
GBS types la. Ib. 11, and 111. Protection studies in mice and chic
embryos were also performed using a group B streptococci
immune globulin (GBSIG). which was prepared fiom human ser
with high titers of type-specific IgG antibody.
MATERIALS A N D METI1OI)S
P R t P A R A T l O N OF HAC'TERIA
GBS Ia-SShl5 (type la) was obtained from the Center f o ~
Disease Control and was passed 2X times in atlult mice nnc
designated la-SS615/2X ( I I). Mouse-passaged strains Ib-H36B/
60/2 (type Ib) and 11-18RS21/67/1 (type 11) were kindly suppliec
by Dr. Rebecca Lancefield. GBS Ib-Grav. 111-And. 111-Bell. 111.
Daw, 111-Grif. and 111-Heat were isolated from infants with GBS
infections.
Bacteria were grown at 37°C to midlogarithmic phase (optical
density of 0.30 at 550 nm) in Todd-Hewitt broth containing 0.5p+
dextrose. Aliquots were frozen in an acetonedry ice bath and
stored at -70°C until used. Viability and concentrations of bacteria (cfu/ml) were determined for each experiment by spread
plating on trypticase soy:53 defibrinated sheep blood agar plates.
~'0L.L.EC'TION AND P R E P A R A T I O N 0 1 . TEST SERA
Pooled 16.5% human G G was obtained from three manufacturers: Cutter Laboratories. Inc.. Berkeley. CA (lot M6352): Hyland Laboratories. Division of Travenol Laboratories. Inc.. Costa
Mesa. CA (lot 0442D01 IAA): and Armour Pharmaceutical Co..
Phoenix, A Z (lot Rl6804). To remove 1gG aggregates prior lo IV
injection into chick embryos. G G was centrifuged at 30.000 rpm
for 3 hr at 4°C and sterilized by passage through Millipore filters
with 0.45-pm pores.
Hyperimmune rabbit anti-GBS type Ill sera were prepared by
immunizing adult male New Zealand White rabbits IV with a
Sormalinized whole cell vaccine of Ill-Bell ( I I). Human sera used
in passive protection studies in mice were obtained from healthy
women and were frozen in I-ml aliquots at -70°C until used. The
human sera were heat inactivated at 56°C for 30 min before use.
The GBSIG was prepared by pooling human sera from five
adult volunteer blood donors with high titers of antibody against
GBS serotypes. Each of the sera had type-specific IgG antibody
78')
PROTECTIVE VALUE 01: GG PREPARATIONS
mg of G G or 0.03 to 4.8 mg of GBSlG in 0. I ml. 0. l to 0.5 ml of
human serum, or 0.05 rnl of rabbit anti-Ill serum 1M 24 hr prior
to lethal IP challenge with GBS. lnocula that consistently produced greater than 90%' mortality were used. Protection studies in
mice with Ill-Bell were also performed inoculating 0.2 ml of
undiluted human sera or 0.125 mg to I mg of G G or GBSlG IP
simultaneously with the IP challenge with 111-Bell. Deaths were
monitored for three days after the bacterial challenge.
At least four chick embryos or mice were given injections of
each dilution of G G or human sera and type of GBS tested. The
mean number of chick embryos tested per dilution of G G for each
of the GBS types was 8, and the mean number of mice tested was
6.5. Protection was designated if at least 75% of chick embryos or
mice survived the bacterial challenge. Controls for each experiment included injection of PBS. bacteria. G G , and protective or
nonprotective human sera with bacteria.
easured by an indirect immunofluorescent ( I F ) assay to at least
le of the GBS serotypes and had titers that were at least twice
e m i n ~ m u mtiter required for chick embryo protection (21). The
ra were pooled in equal amounts, and the IgG fraction was
3tained by (NH4)2S0.tprecipitation and DEAE-cellulose chroatograph; (8). Using membrane filtration (CF5OA membrane
Ines; Amicon Corp.. Lexington, MA), the GBSlG was concenated to a protein concentration of I to 5 g/100 ml as determined
y the Biuret reaction. Purity of GBSlG was demonstrated by
!~nlunoelectrophoresis.
The IF assay for type-specific Igti antibody to each ofthe GBS
:rolypes utilizes acetone-fixed whole bacteria on slides and mono~ecificrabbit antihuman IgG conjugated with fluorescein isothiLyanate ( 2 1 ).
RESULTS
A N I M A I . STU1)lES
The LD,, and LD!xl in 12-day-old chick embryos for the type
111 GBS strains, Ill-And. 111-Daw, Ill-Grif. and Ill-Heat, are
shown in Table I . Susceptibility of 2 I-day-old mice to IP challenge
with CiBS Ib-Grav. lb-H36B/60/2, 11-IXRS21/67/1, 111-Bell, and
Ill-Daw is shown in Table 2.
The minimal amount of G G or GBSlG necessary to protect
chick embryos against GBS types la. Ib, 11. and 111 is shown in
Table 3. Protection studies were not performed with type Ic GBS
because of our previous finding that protection of chick embryos
by human sera is nearly identical for types Ia and Ic (21). Chick
embryos were protected against IV challenges with type Ia-SS615/
28 by the simultaneous 1V administration of all three G G preparations at doses of 0.4 to 0.8 mg. For types Ib-H36B/60/2 and II18RS21/67/1. 1.65 mg of all three G G preparations failed to
protect chick embryos. G G from two of three manufacturers
protected chick embryos against type Ill-Bell at doses of 0.4 and
1.65 mg.
Mice inoculated IP with type la GBS were protected by the IM
administration of 0.5 to 1.0 mg of all three G G preparations
(Table 4). For type Ib-H36B/60/2, mice were protected by two of
three G G preparations given IM at doses of 0.5 and 1.0 mg.
Because the LD,,, of Ib-H36B/60/2 inoculated IP into mice was
Twelve-day-old chick embryos were inoculated IV with 0.1 ml
f a mixture contain~ngequal volumes of a lethal inoculum of
iBS diluted in phosphate-buffered saline, pH 7.2 (PBS) and G G
r GBSlG (18). The 50':i lethal dose (LD:,l) and Y0"i lethal dose
LD!",) for la-SS615/2X. lb-H36B/60/2. 11-18RS21/67/1. and 111;ell have been reported previously (18. 21). The LD:,,' and LD:nl
f 111-And. 111-Daw. Ill-Grif, and Ill-Heat were determined by
robit analysis of dose mortality curves established by IV inoculaon of c h ~ c kembryos with increasing numbers of bacteria in 0.1
11. The inoculum of GBS used in passive protection studies in
h ~ c kembryos was one to two times the LD!,,. t i G was diluted I /
. I / 10, 1/20. and 1/40 with PBS. which resulted in the inoculation
f 1.65. 0.8, 0.4, and 0.2 mg of G G into chick embryos, respecively. The GBSlG was diluted with PBS so that the amount
njected was 0.4. 0.2. 0. I . 0.05, and 0.025 mg.
The bacterial inoculum that consistently produced greater than
0"; mortality in 21-day-old mice was established by 1P injection
rf increasing numbers oflb-Grav. Ib-H36B/60/2, and 11-18RS2I/
17/1 in 0.2 ml of PBS, Ill-Bell. and Ill-Daw in 1.0 ml of heart
nfusion ( H I ) broth with 5':; defibrinated sheep blood (5). Passive
mtection studies in 2 I-day-old mice challenged with la-SS6 15/
!X have been described previously (15). Mice received 0.25 to I
Table I . Su.sceptihi11f~~
ofI2-do!-old chick
ernhrvos to !,pe 111 G B S
.-- -.--~
-~
0/4
-~
~~
Ill-And
(dead/~njected)
---
Ill-Grif
(dead/injected)
1 1/22 (50)
9/16 (56)
12/20 (hO)
9/12 (75)
4/4 (100)
4/4 ( lo())
24 cfu
106
cfu
-~
(0)'
11/22 ( 5 0 )
X / I X (44)
4/4 (100)
Ih/2h ( 0 2 )
39/4h ( 8 5 )
4/4 (100)
41 ct'u
1x7 ct'u
ND
I X cfu
I20 cfu
X/X
-
~
-
---
Ill-Daw
(dead/injected)
(
-
-
~
Ill-tfedt
(dead/lnjected)---
-
- -
I(H))
-
-
-
3/Y
-
humhers in parenthears. "i mortality
' N 1). not done.
I
-
ctu
lnjected
I x loI x lo',
x 10'
l x I0
I x lo'
I x lo'
5
Ib-(~rdc'
(dedd/lnjected)
X/X (100)'
X / X (100)
N L)
18/20 ( Y O )
Table
2 S u ~ t e p r r h ~ hof
t , 21-dm-old
mlce to GBS
---
-
-
Ib-H3hH/h0/21
(dedd/lnjected)
-
17/18(94)
4/X (50)
ND
3/X (37 5)
1/4 (25)
2/X (25)
--
11-IXKS21/67/1'
(dead/~njected)
N DJ
11/12 (I(X))
15/16 (94)
1O/12 (81)
4/12 (33)
-
-
--
-
Ill-Brll
(dedd/lnjected)
--
X/X
(100)
22/24 (92)
N I)
10/16 (h2 5)
6/X (75)
2/8 (25)
1/4 (25)
ND
0/4
(0)
-I Ib-(rrdv. lb-l136B/h0/2. and 11-IXRS2l/h7/1 were d~lutedIn PBS dnd ~noculdtedIP Into mlce In O 2 rnl
' Ill-Bell and Ill-llaw were diluted in HI broth with sheep red blood cells and inoculated IP into mice in 1.0 ml.
' Numbers In parentheses. '; mortality.
' N I). not done.
-
--
-
-
-
(33)
Y / I I (82)
N 114/4 (100)
4/4 (100)
19 cfu
59 ctu
--
790
VOGEL ET A l .
large, Ib-Grav, with a smaller L D y l . was also used in mouse
protection studies. and G G from only one manufacturer protected
mice at a dose of I mg. For 11-18RS21/67/1, none of the GCi
preparations protected mice. Using IP inoculations of 111-Bell or
111-Daw in 1 ml of HI broth with sheep blood. IM administration
of I mg of any of the three G G preparations failed to protect mice.
In mice challenged IP with a lethal dose of Ill-Bell in 1 ml of
HI broth with sheep blood, simultaneous IP administration o f 0.7
ml of human sera with IF titers of I:XO or greater protected mice.
Table 3
-
-
-
-
-
-
-
--
-
-
-
lb-H36B/60/2
-
11- IXRS21/67/1
40
0/ 12'
200
2/20
6/8
9/12
3/8
0/4
0/4
h/X
X/X
IS/lX
2/8
4/8
5/X
I /X
I /x
-
-
7/X
7/x
7/16
3/8
4/8
3/8
6/12
1 /4
4/11
4/8
0/4
7/x
7/X
8/X
8/X
8/x
R/X
X/X
X/X
7/X
7/X
7/X
7/X
x/X
-
-
lnoculum (cfu)
Control'
GG
Armour (mg)
1 65
0X
04
C utter (mg)
165
0x
04
02
Hyland (mg)
1 65
08
04
GBSIC; (mg)
04
02
0 1
0 05
0 025
-
P u ~ ~ r v e p r o r e t i r oon
f thrch e m h r r o ~nrrh GG und
-
la-SS6 15/28-
However, none of the GG preparations inoculated IP at a dose I
1 mg protected mice against simultaneous IP challenge with 11
Bell.
Because none of the three G G preparations protected mice (
chick embryos against all four GBS serotypes tested, a GBSIt
was prepared from selected immune human donors. Table 5 shou
the antibody titers by IF to each of the GBS types. each of tt
five constituent human sera. GBSIG, and in the G G preparation
Administration IV of 0.2 mg of GBSIG protected chick embryc
-
Ill-And
175
2/16
175
1 /20
100
0/4
175
0/4
4/12
2/x
2/X
10/12
3/12
l/X
9/11
h/X
h/X
0/4
-
-
-
-
-
Ill-llaw
-
8/X
6/12
4/8
GBSlG
Ill-Bell
-
-
-
-
-
-
-
-
-
-
-
-
-
4/4
4/4
-
7/X
-
-
4- /4
3 /4
X/X
-
- -
,
-
-
-
-
-
-
-
Concurrent control? glven Injecttons of bdcter~aand PBS
- Number of chlck embryo\ ~urvlring/numberof chlck embryos glven tnjectlons
' Protect~on~ t u d ~ ewere
a not performed
I
-
-
-
-
-
-
-
lnoculum (cfu)
Control<; G
Armour (mg)
10
05
0 25
C utter (mg)
10
05
025
Hyldnd (mg)
10
05
0 25
CIBSIG (mg)
4X
10
05
0 25
0 I2
006
0 03
--
I
-
-
-
Table 4. Pur~rveprotectron
of
-
-
-
Id-SS6 15/28
-
2
-
-
-
-
--
x lo'
I x lo‘
2/16
1/12
I
4/8
1 /4
4/8
-
I
-
-
GG und GBSIG
--
-
11-1XRS2l/67/ 1
- --
-
-
-
Ill-Bell
-
5 x 10
2/20
I x lo''
1/16
0/ X
3/16
-
6/8
0/4
4/4
7/X
1/ X
4/4
4/x
4/4
3/8
6/X
4/X
3/8
-
Z/X
7/12
0/4
-
-
3/X
2/11
-
-
-
-
-
4/4
4/4
4/X
4/4
4/4
4/4
7/8
7/8
-
mlte nrth
-
-
-
-
Ib-Grdv
10'
1/16'
X
7/x
1 /4
-
-
Ib-H36B/60/2
- -
-
-
-
M I L inoculated
~
IP ~~multaneou\ly
w ~ t hIll-Bell and G G
Concurrent control\ given injections of hacterld and PBS
I Number of mlce surv~vtng/numberof mlce glven Injecttons
Protect~onstud~eswere not performed
-
I/X
-
-
4/4
8/X
7/8
5/X
-
4/4
4/4
4/4
5/20
-
o/X
1/ X
0/4
-
-
-
-
Ill-Bell(IP)'
-
1
x 10"
1/12
70I
PROTECTIVE VALUE 01- CiCi PRLPARATIONS
Table 5
Antrhod, trter, of GBSIG conttrtuent human sera,
pooled GG
and
-
-
Ant~bodyttter'
-
la
Ib
Ic
II
I60
10
160
20
40
I60
I60
I60
40
40
Ill
era
ianima globulin
Armour
('utter
Ilyland
I60
~
~
X0
20
- -
I60
40
-
' Antihody tlter measured by IF to <iBS types la. Ih. Ic. 11. and I l l .
Rec~procaltiter or individual human serum.
' Antihody not detected in und~lutedsera hy IF
Reciprocal titers of a 16.Sr; preparation ofGRSI<i.
gainst lethal IV challenges with all strains of the tbur GBS types
:sled.
The IM administration of GBSIG protected mice against IP
hallenges with types la. Ib. and I1 GBS strains at doses from 0.03
:, 0.5 mg. As much as 4.8 mg of GBSIG administered IM failed
3 protect mice challenged IP with 111-Bell. The IM administration
f u p to 0.5 ml of a human serum with an IF antibody titer to
ype I11 of 1:640 also failed to protect mice against IP challenge
vith 111-Bell. with four of eight mice surviving. In contrast. 0.05
nl of hyperimmune rabbit anti-Ill serum administered IM proected all four mice against subsequent IP challenge with Ill-Bell.
astly, the simultaneous administration of 0.25 mg of GBSIG
vith 111-Bell IP protected all b u r mice tested.
Until an effective and safe vaccine is developed and distributed
br all five GBS types. passive immunizatio; could be a useful
llternative for the prevention of neonatal GBS infections. EarlyInset GBS infections could be prevented by the administration of
> G to mothers or neonates in pregnancies associated with a high
isk of neonatal GBS infections ( I . 16). Because early-onset GBS
nfections are often acquired in utero ( I , 16). administration of
3 G to the mother prior to or during labor may be useful in
,reventing or attenuating these infections. Alternatively. passive
mmunization could be given at birth to neonates who are at high
.isk of developing early-onset GBS infections. Because recurrent
3BS infections in neonates have been a problem (6. 19. 22).
Iassive immunization may be worthwhile i n preventing recur-ences after completion of antimicrobial therapy. Passive immulization may also be of value in the prevention of late-onset CjBS
nfections in colonized infants who lack protective levels of typeipecific antibody.
Despite appropriate antibiotics, the mortality of early-onset
3 B S infections is approximately 50% ( I ) . Shigeoka et al. (14) have
presented preliminary data suggesting benefit from transfusing
~nfantswith fresh whole blood containing heat-stable. type-spe:ific opsonins in the therapy of early-onset GBS infections. All
nine neonates who received blood containing antibody to their
~nfectingstrains survived. but only three of six infants survived
who were transfused with blood lacking homologous type-specific
antibody. An increase of type-specific opsonic activity was only
observed in neonates who received a transfusion of at least 40% of
their blood volume. Similarly. G G could also be used as an
adjunct to antibiotic and supportive therapy in GBS infections.
The advantages include administration to small neonates In acceptable volimes. thus avoiding transfusion. and a defined antibody content.
We have evaluated prophylactic G G and GBSlG in two experimental animal models of GBS infection. G G from each of three
manufacturers failed to uniformly protect chick embryos or mice
against lethal infections with all of the four GBS types tested. This
result was not surprising because we have found that only a small
percentage of sera from adults possess type-specific IgG antibody
which protects chick embryos ( 2 0 ) . Therefore. GBSIG was prepared from selected immune donors.
The simultaneous IV inoculation of GBSIG with GBS-protected chick embryos against all strains of the four GBS types
tested. T o estimate the amount of GBSIG in a human neonate
that is equivalent to the protective dose of GBSlG in the chick
embryo. we assumed blood volumes of 1.5 ml in 12-day-old chick
embryos (13) and 85 ml/kg in human newborns (12). Inasmuch
as the blood volume per kg in human newborns is approximately
60 times greater than in chick embryos. GBSIG. I2 mg/kg (0.07
nil/kg of a 16.5 g V preparation) would be roughly equivalent to
0.2 mg of GBSlG that is protective in chick embryos agatnst each
of the-four types tested.
Mice were protected against lethal 1P challenges with types Ia.
Ib, and 11 GBS by the IM administration of0.5 mg of CiBSIG. In
contrast, IM administration of4.X mg of GBSlG failed to protect
mice against IP challenges with type 111 GBS. and protection was
observed only when GBSIG was administered simultaneously IP
with 111-Bell or when hyperimmune rabbit sera was given IM. The
inability of IM-administered GBSlG to protect mice challenged
IP with 111-Bell may be explained by differences in murine resistance to type 111 GBS (10). Because the mean weight of the mice
was 10 g. the IM dose of GBSIG was 50 mg/kg or 0.3 nil/kg of
preparation for protection agains; types la, Ib, and 11.
a 16.5
The four-fold increase in GBSlG needed to protect mice compared
to chick embryos probably reflects the differences in the route and
timing of adrninistration. Protection was more readily attained
when GG was mixed with bacteria immediately before IV injection into chick embryos than the IM administration of CiCi 24 hr
prior to IP bacterial challenge in mice.
These studies indicate that a hyperimmune globulin may be
effective in preventing human infections with all of the CiBS
serotypes. Our results also suggest that, along with obvious theoretical advantages, an IV preparation would be superior, but
en~yme-treatedIV G G has not been approved for routine use.
CiBSICi is a potentially useful agent in preventing neonatal GBS
infections, as well as a possible adjunct to antibiotic and supportive
therapy of severe GBS infections. These studies demonstrating
effectiveness in two animal models of GBS infections justify tr~als
in human neonates.
if%)
I
?
3
4
5.
6
7.
X
9.
I0
Baker. C' J Summar! of the workshop o n p e r ~ n a t a l~ n l r c t ~ o nd ru e tu group B
.Yrrc.proi.oi.<.lr. J I n k c t . [)I\. 136 137 ( ILj77)
Baker. C ' J., t d w a r d s . M. S , a n d Ka\per. D. 1.. I r n m u n o g e n ~ c ~(11
t r pcilysacchar ~ d e \Iron1 type Ill. group B S r r c . p r o ~ o i ~ ~J ~ (u'\l ~ n Invest . h l 1107 ( lV7X)
Baker. ( ' J . and K;i\per. 1) L I r n m u n ~ ~ l o g ~ Invcrtlgatlon
cal
(11 l n l j n t s u ~ t h
\r[,tlccrnl:l <,r n~entnpltl\c l ~ t eI < ? grtwp R Srr?pro~.o,,.!r$J Infi.cl
Stlppl .
136 SVX ( Ic)77)
Baker. C'. J.. Kasper. I) L . Tager. I . B Parede\. A,. Alpen. S.. McC'<irmack. W.
M . a n d <;ort>lt: I ) . Q u a n t ~ r a t ~ vdetermtnatlun
e
ul a n r ~ h o d yto cap\ul.ir pol?r a c c h a r ~ d eIn lnlectlon w ~ t htype 111 \tralna of group B Srrc.proi.(?wzr\ J C'l~n
Invert.. CV X 10 ( 1977)
Balt~rnore.R S.. Kasper. D I... a n d Vecchltto, J S: Mouse prorectlon te\t lilr
group B Srrepro<~occu\
type Ill. J Infect. I)'\. 140 X I ( l1,7O)
Broughton. D. D.. M~tchell.W (i <iro\\man. M Hadle). W K . a n d ('ohen.
M S. Recurrence o f group B \treptococcal ~nl'ectlon J Pedlatr. H'J 1x3
( I V70J
Hernmlng. V (i . tiall. K 'T. Khode\. P C i . S h ~ g e o k a .A 0.. a n d l1111, t i K
Asse\srnent ol group B streptococcal op\onln\ In h u m a n a n d r a h h ~ tw r u m h!
neutrc,ph~lc h c m ~ l u r n ~ n e r c e n cJe ( ' l ~ n Invert. 7.Y 1379 (IV7h)
Kahat. t A Kahat and Meyer'\ Experlrnental Imrnunochern~stry Znd ed
(('harles ( ' Thomas. Spr~nglield.11.. I97 1 ).
Krerrchmer. K K.. a n d (iutofl, S. P . lrnmunolog~calaspectr ol group B \[reptc,coccal ~ n k c t l o n s I n l i c t ~ o n h, 146 ( l97X).
Kret\chrner. R K . Vogel. I. ( ' . Kelly. P . Padno\. D . (ioldman. M . a n d (;atoll.
.
.
.
VOGEL ET A L.
II
I?
I?
I4
I5
16.
17
IX
S. P M e c h a n ~ s mof mouse resistance to group B streptococci ((;BS) type Ill
I!\h\tract). Sebenth lnternatlonal S y n ~ p o \ ~ uon
m Streptoioccl a n d S t r e p t w w cal I)~\eases N o 147 ( IV7X)
1-ancelield. R. C . Mecarthy. M . and tverly. W N. M u l t ~ p l emouse-protect~\e
a n t ~ h o d ~de~s r e c t e dagarnst group B \treptococcl: \peela1 reference to a n t ~ h o d l e s
e l l e c t ~ v eagaln\t proteln antlgens J . E.xp. Med.. 142 Ih5 (1975).
M o l l ~ \ o n .P L . Veall. N . and Cuthush. M. Red cell and plasma \olume In
newhorn Infant\ Arch Dl\ Child . 3 242 (1950)
R ~ r m a n o l l .A I. T h e A v ~ a nt m h r y o Structural and Functional D e ~ e l o p m e n t
( T h e M a c M ~ l l a n('ompan). New York. 1960)
S h ~ g e o k a .A 0 . Hall. R T . and HIII. H . R.. Blood-translis~on In group-B
\trept<>cc>ccal\ep\lr Lancet. I 636 ( 107X)
Stewardson-Krleger. P B.. Alhrandt. K.. Nevln. T.. Kretrchmer. R . R.. a n d
(;atoll: S P Perlnatal lmmunlty to group B fi-hemolyt~cSrreptoc.occu. type
I:I J lnlrct I l l \ . 1 in M V (1977)
S t r ~ a r d s o n - K r ~ e g ePr . B and ( i o t o K S P R ~ s kfactor\ In early-onset neonatal
group B strept~ti(tica1~nfectlons.Inf'ect~on.n 50 (1978)
Stlehm. t R Standard and speclal human Immune serum glohullns as therap e u t ~ cagents P e d ~ a t r ~ c6.l:
s . 301 ( 1979)
Tlellenherg. J . V<igel. L . Kretschmer. R . K.. Padnos. D . and ( i o t o l l S P.
(.hlckem emhryo m < d e l Ibr type 111 group B heta-hemolytlc streptococcal
\eptlcemla Inltct. l m m u n . l V . 4x1 (1978).
.
c
Foundation. Inc
( ' r ~ p y r ~ g hV)t 19XO I n t e r n a t ~ c ~ nPa le d ~ a t r ~Research
IN)? I -?9uX/XO/ 1405-07XXS~)~.lW1/0
I9 Truog. W , t . . Davls. K F.. and Rav. C . <i Recurrence of group B streptocctis
~nfectlun.J . Ped~atr..X V 1x5 (1976).
211 Vogt.1 1. ('.. Kretschmer. R . K.. Buyer. K . M . Padno\. D M . (;adlala. C'
and (;atoll: S. P.. Prevalence of group B strept~ticticala n t ~ h o d ymeasured
lndlrect ~mn~unofluorescencePedlatr. Kes. (Abstract). I . ( . 470 (1979)
? I . Vugel. 1. (' . Kretschmer. R K.. Boyer. K M.. Padnos. D M tiadrala. C'
and (;atoll: S. P: t i u m a n lmrnunlty to group B rtreptococc~ measured
l n d ~ r e c t ~ n ~ m u n ~ i f l u o r e s c e n ccorrelat~on
e.
w ~ t hchick e m h n o protection.
lnlrct D l \ . 1411 6x2 (1079)
22 Wt~lker.S t i . Santoa. 4 . Q . and Qulntero. B. A.. Recurrence ol group B
streptoeweal menlngltls J Ped~atr..X V . I87 ( 1976)
23 T h e author\ thank D r Arrnando R. Orllna. M e d ~ c a lD ~ r e c t o r01 the Mlch;
Reese l l ~ ~ a p ~Blood
t a l Center, lor his cooperahon and Madellne Murphy I
excellent \ecretarlal \upport
24 Request, I l ~ rreprint\ \huuld he addresbed to. Samuel P. Ciot~>ll:Ilepartment
Pedlatr~c\.M ~ c h a e lRee\e t i o s p ~ l a land Medical Center. 29th Street and El
.Avenue. ('hlcago. 11. 6Ohlh ( U S A )
25 T h ~ sresearch was supported hy Puhllc Health Service grants KO-I-HD-0'47
and K O - I - H D - I I576 from the National Inst~tuteoI'('h11d Health and H u m
De\el<~pnlent.
26 Reeelbed lor puhl~catlonA p r ~ 23.
l 1979
27 Accepted l i ~ rp u h l ~ c ; ~ t ~July
o n 31. 1979
.