CHOLERA VACCINE

Cholera is caused by the bacterium Vibrio cholerae. Active immunization against cholera has been achieved with some success by vaccines. Vaccination is not recommended to control ongoing outbreaks. Oral cholera vaccine is only recommended for populations at immediate risk of a cholera epidemic. The various vaccines that have been employed over the years to prevent cholera can be divided into four types. 

Killed parenterally administered vaccine:
Consists of a heat-killed, phenol-preserved mixed suspension of Inaba and Ogawa subtypes of Vibrio cholerae, Serovar 01. It is given in two-three subcutaneous or intramuscular doses separated by 1-6 weeks. Booster doses may be given every six months. The vaccine provides 50% efficacy, which lasts for 6-12 months. Approximately 50% of vaccine recipients develop a soreness and inflammation at the site, and 10 to 30% develop generalized symptoms of fever and malaise. Symptoms usually last one to three days. It is poorly immunogenic in children. This vaccine is no longer recommended for use.

Killed orally administered vaccine:
The vaccine is prepared from four strains of killed V.cholerae, including a heat-killed classic Inaba, a heat-killed classic Ogawa, a formalin-killed El Tor Inaba and a formalin-killed classic Ogawa. The vaccine (WC/rBS) is killed whole V. cholerae 01 in combination with purified recombinant B subunit of cholera toxin. The vaccine must be diluted with and given with fresh clean water. The vaccine should be given in two doses 10 -14
days apart. Immunity is conferred within one week of the second dose. After 2-3 doses there is good mucosal IgA antitoxic and antibacterial antibody levels. There may be 50%-60% protection for at least three years for all age groups. However, protection in children aged <5 years may decline more rapidly after 6 months. Protection is not conferred against V. cholerae O139. It has also been shown to be safe in pregnancy and breast feeding. This vaccine is being used in Latin American countries. Mild post-vaccination gastrointestinal symptoms have bee reported. 

Live attenuated oral vaccines:
These attenuated strains multiply in small intestine and stimulate both local antibacterial and antitoxic immunity.
1. Texas Star: It is a chemically attenuated mutant with missing A subunit. It requires single dose but adverse reactions along with potential reversion to virulence resulted in its discontinuance. 
2. JKB 70 and CVD 101: These strains were produced by deletion of gene coding for A subunit. Both strains colonized small intestine and induced good immune response, but caused mild diarrhoea and abdominal cramps. They are no longer used.
3. CVD 103 HgR: An attenuated live oral cholera vaccine, containing the genetically manipulated V. cholerae 01 strain that is a derivative of classical biotype Inaba serotype strain 569B. Unlike previous attenuated strains, it does not produce enterotoxin, SLT or hemolysins. It has minimal reactogenicity but low colonization potential and therefore has to be given in higher doses. 5x10^8-9 lyophilized and buffered vibrios in water are ingested at empty stomach. A single dose must be given with clean, fresh water. The protection is effective from age 2 and lasts for six months in 60-90% of vaccines. The vaccine provides similar protection levels as the WC/rBS for all age groups after seven days of administration, but this may drop sharply after 6 months. Following administration of the currently licensed CVD 103-HgR strain, gastrointestinal symptoms were reported. It does not provide protection against infection with O139 vibrios.

Other vaccines:
1. Subunit vaccine consisting of synthetic peptides of subunit B
2. Idiotypic vaccine, from antibody against cholera toxin
3. Hybrid vaccine, with Salmonella ty21a