HUMORAL IMMUNITY IN MALARIA 
By L. T. COGGESHALL 
LABORATORIES OP THE INTERNATIONAL HEALTH DIVISION, ROCKEFELLER FOUNDATION, NEW YORK 
The humoral aspects of immunity in 
malaria, like those of any other infectious 
disease, are concerned with the production 
and behavior of specific antibodies, the 
study of which has been handicapped 
chiefly by the lack of a method of cultiva¬ 
tion or a suitable means of concentrating 
the malarial plasmodia. This is especially 
true with those species pathogenic for man, 
which, incidentally, present an additional 
difficulty as they are not known to be in¬ 
fectious for a lower animal. In spite of 
these difficulties, it has been conclusively 
demonstrated that the development of im¬ 
munity in malaria is accompanied by the 
development of specific antibodies in the 
circulating blood. The identity, nature 
and mode of action of the various anti¬ 
bodies thus far shown to be directly con¬ 
cerned with recovery from an acute attack 
or relapse in malaria have been obtained 
almost entirely from the study of the dis¬ 
ease in lower animals. However, since the 
behavior of most of the experimental infec¬ 
tions, especially those occurring in mon¬ 
keys, closely resembles that of the disease 
observed in man, important inferential 
evidence may be obtained. 
Passive Immunity 
The early attempts to transfer passively 
protective antibodies in malaria were based 
upon the use of convalescent serum ob¬ 
tained from patients with long standing 
chronic infections. Soteriades (1917) ob¬ 
tained serum from patients who presum¬ 
ably had a high degree of immunity, as 
judged by the presence of circulating para¬ 
sites, and no clinical symptoms. He ad¬ 
ministered this serum to another patient 
during an acute attack and reported im¬ 
provement in the recipient. More recently 
Lorando and Soteriades (1936, 1937), re¬ 
peating the experiments with whole blood, 
have reported that a beneficial effect is 
obtained when this procedure is used as 
a therapeutic measure. Kauders (1927) 
showed that serum obtained after recovery 
from attacks of induced malaria would 
ameliorate an active infection in paretics 
and that acute or normal human serum 
was entirely ineffective. These experi¬ 
ments suggested the presence of circulating 
protective substances but were not conclu¬ 
sive since the effects could have been non¬ 
specific or entirely coincidental. 
Protection tests in animals were at¬ 
tempted by numerous investigators with 
consistently negative or inconclusive re¬ 
sults until it was shown by Coggeshall and 
Kumm (1937) that the serum of rhesus 
monkeys with chronic P. knowlesi malaria 
protected normal monkeys against death 
due to infection with this very virulent 
parasite. In the same study it was dis¬ 
covered that homologous immune serum 
would attenuate the less severe P. inui in¬ 
fection and that normal serum was entirely 
without effect against either infection. 
There is a quantitative relationship be¬ 
tween the amount of immune serum and 
the number of parasites used in the in¬ 
oculum for a protection test; smaller 
dosages of parasites require proportionally 
lesser amounts of immune serum for effec¬ 
tive protection. (Coggeshall and Eaton 
1938b). This is a probable explanation for 
earlier failures with protection tests in that 
dosages were excessive and overwhelmed 
the action of the antibodies. More recently 
Hegner and Eskridge (1938), Manwell and 
Goldstein (1940), Mosna (1938), and Talia¬ 
ferro and Taliaferro (1940) have also been 
able to demonstrate that the serum of ani¬ 
mals with chronic malarial infections con¬ 
tained protective antibodies. The blood 
serum obtained from paretics after induced 
P. knowlesi malaria exerts a protective 
