Russian vaccines against especially dangerous bacterial pathogens

Figures & data

Table 1 Licensed human EDP vaccines in Russia

Disease	Vaccine	Strain	Protective effect in humans	Duration of immunity	Frequency of prophylactic inoculation (humans)	Route of immunization, immunization dose in CFU (approved in protocol for human vaccination)		Number of doses in ampoule for adults/concentration of bacteria in ampoule, minimal % live bacteria required	Manufacturer
Plague	LPV (LWC)	Y. pestis EV line NIIEG attenuated (lyophilized), Pgm^−, pMT^+, pCD^+, pPCP^+	Protective against bubonic and pneumonic plague caused by wild-type Y. pestis strains	From day 4 post inoculation up to one year	Single injection annually	Suspension for injection	Cutaneous (scarification)—3.0×10^9 in 0.15 mL; Subcutaneous—3.0×10^8 in 0.5 mL; Intradermal—3.0×10^8 in 0.1 mL; Inhalation—(2.0–8.0×10^6)	2 mL with 80–430 doses/5×10^10–1×10^11CFU, ≥25%	Stavropol API Russia; M. Aikimbayev’ Kazakh Science Centre for Quarantine and Zoonotic Diseases of Ministry of Health, Republic Kazakhstan, Almaty
						ODT for oral use	Lingual for mouth dissolving—(40±10)^9	(40±10)^9, either 40 or 90 tabs	Research Institute for Microbiology, Kirov, Russia
Anthrax	LAV STI-1 (LWC)	B. anthracis STI-1, attenuated (lyophilized), non-capsulated, pX01^+ pX02^−	Protective against cutaneous, inhalational and gastrointestinal forms of anthrax caused by wild-type strains of B. anthracis	One year	Single s.c. injection annually	Cutaneous (scarification)—5.0×10^8 CFU/spores in 0.05 mL glycerol water 30% solution; Subcutaneous—5.0×10^7 CFU/spores in 0.5 mL 0.9% sodium chloride		Either 20 doses with 1.5 mL solution medium (30%) glycerol water solution for cutaneous immunization or 200 doses for subcutaneous injection; Either 10 doses with 1.5 mL solution medium (glycerol water solution 30%) for cutaneous immunization or 100 doses for subcutaneous injection/(4–6)×10^9 spores, ≥ 40%	Research Institute for Microbiology, Kirov, Russia
	Combined STI-1+PA (LAV, LWC, STI-1 combined with PA adsorbed on aluminum hydroxide)	B. anthracis STI-1, attenuated (lyophilized), noncapsulated, pX01^+ pX02^−	Protective against cutaneous, inhalational and gastrointestinal forms of anthrax caused by wild-type strains of B. anthracis	One year	A single s.c. injection annually first three years, then—a single injection every two years Revaccination: first three injections annually following a single vaccination every two years	Subcutaneous—0.5 mL		10 doses, with 6.0 mL solution medium	State Orel Biofactory, Russia
Tularemia	LTV (LWC)	F. tularensis 15 NIIEG attenuated (lyophilized), the parental strain for LVS	Protective against bubonic, gastrointestinal, pneumonic, oculoglandular tularemia	10–12 days post immunization up to five years	A single injection in five years	Cutaneous (scarification)—2.0×10^8 in 0.1 mL; Subcutaneous/intradermal—1.0×10^7 in 0.1 mL		100 doses for cutaneous and 2000 doses for intradermal (2±1)×10^10; 80%	Federal State Scientific-Industrial Company MICROGEN, Omsk, Russia
Cholera	Vaccine cholera bivalent chemical tableted (VCBCT)	V. cholerae O1 569 B (Serovar Inaba, Biovar Classic) and V. cholerae O1 M-41 (Serovar Ogawa, Biovar El-tor)	Protective against cholera classical and El-Tor	6–7 months	As necessary	Tablets Oral, 1 dose for adult—either 3 tabs of concentration [CTB(100 000±20 000 BU) in combination with 10 000 BU O antigen Inaba+O antigen Ogawa ] or 6 tabs of concentration [CTB (50 000±1 0000 BU) in combination with 5000 BU O antigen Inaba+O antigen Ogawa]		1 tablet—either [CTB (100 000±20 000 BU) in combination with 10 000 BU O antigen Inaba+O antigen Ogawa ] or [CTB (50 000±10 000 BU) in combination with 5000 BU O antigen Inaba+O antigen Ogawa]	API ‘Microbe’, Saratov, Russia
Glanders	KGCAV (KWC)	Avirulent strain B. mallei number 11	Protective against local cutaneous and pulmonary glanders caused by wild-type strains of B. mallei	One year	Annually	Suspension for injection subcutaneous—4×10^9 in 0.5 mL		6 doses, 3.0 mL	Research Institute for Microbiology, Kirov, Russia
Brucellosis Prevention of brucellosis in humans	LBV (LWC)	Brucella abortus strain 19-BA attenuated (lyophilized)	Protective against infections, caused by B. melitensis, B. suis and B. abortus/Cross-protective against B. melitensis and B. suis, less than against B. abortus	20–30 days post injection up to one year	Annually Revaccination: cutaneous (scarification)—0.5×10^9 in 0.1 mL	Prime injection: cutaneous (scarification)—1×10^10 in 0.1 mL; subcutaneous—4 ×10^8 in 0.5 mL Revaccination: cutaneous (scarification)—0.5×10^9 in 0.1 mL		4–10 doses, 1 mL (7.0±3.0)×10^10, >60%	Federal State Scientific-Industrial Company MICROGEN, Omsk, Russia
Therapeutic	LBV inactived (KWC)	Combined/mixed two virulent strains Brucella melitensis and 1 strain Brucella abortus (1:1:1) inactivated by heating; fluid suspension for injection	—	—	Annually	Suspension for injection Intradermal injections—accelerated doses in zones of joints (either ulnar or knee) at a distance of 40–60 mm from each other; minimal dose: 2×10^5, maximal dose: 3×10^8 depending of individual clinical features		1×10^9 in 1.0 mL	Research Institute for Microbiology, Kirov, Russia

Abbreviations: BU, binding units; CTB, cholera toxin B subunit; KGCAV, killed glanders whole-cell adsorbed vaccine; KWC, killed whole-cell; LAV, live anthrax vaccine; LWC, live whole-cell; ND, no data available; ODT, oral dissolving tablets; LBV, live brucellar vaccine.

Table 2 Possible post-vaccine side effects and contraindications in vaccinees for the Russian vaccines against the EDPs

Diseases	Possible side effects, duration	Contraindications
		Typical	Specific
Plague	Local: 1–2 days after immunization—edema, hyperaemia, skin vesicular eruption at the site of inoculation	Systemic: 1–3 days after immunization—malaise, headache, increased body temperature up to 37.5 °C, in 1% vaccinees—up to 39 °C in some	Acute infectious and noninfectious diseases; systemic connective-tissue diseases; malignant neoplasms; immunodeficiency; allergy and hypersensitivity	None
Anthrax	Did not produce serious/pronounced local or systemic adverse effects in vaccinees	Dermatoses and endocrine diseases
Tularemia	Local: hyperemia & edema (d 1–15 mm) 4–10 days post injection, produced by each vaccination by cutaneous route; sometimes a short-term swelling and painfulness of regional lymph nodes; mildly pronounced/marked hyperaemia and edema (d up to 40 mm)	Systemic: none	Individuals who have had tularemia and positive serological or skin tests for tularemia
Cholera	Local: slight discomfort in the epigastric region after 1–2 h post immunization; borborygmi and mushy stools that pass quickly and do not require treatment	Systemic: none	Gastrointestinal dysfunction
Glanders	Local: none reported	Systemic: none reported	None
Brucellosis Prevention of brucellosis in humans	Local: 1–2 days after immunization—hyperaemia, skin vesicular eruption or infiltrate at the site of inoculation	Systemic: 1–3 days after immunization in 1%–2% vaccines—malaise, headache, increased body temperature up to 37.5–38 °C	Recent brucellosis	Positive serological and skin tests for brucellosis
Therapeutic	Local: none	Systemic: increased body temperature up to 37.5–39.5 °C, light fever exacerbates pain in the lesions	Decompensated cardiovascular diseases; hemorrhagic diathesis; organic lesions of the central nervous system; chronic diseases, acute flare-ups

Abbreviation: d, diameter.

Table 3 Vaccine manufacturing requirements

Infection/diseases	Regulatory Documentation #	Industry standard sample #	Indicators and characteristics
			Main biological characteristics	Safety and immunogenicity (animal model)	Percent of live bacteria required in an ampule (%)	Retention period of the reference vaccine strain (year)
Plague	FSP LSR-005759/08-220708	42-28-392-11	General biological properties; typical of Y. pestis; ‘residual virulence’; innocuity test; protective efficacy; concentration of live bacterial cells; strain properties- Pgm^−, pMT^+, pCD^+, pPCP^+; thermostability ≥4 days	Guinea pigs and albino mice	≥25	10
Anthrax	FSP 42-1376-06	42-28-376-10	The absence of a capsule and hemolysis	The morphology of ‘pearl necklace’ Concentration of live bacterial spores ≥90%	Rabbits and guinea pigs	40	10
Tularemia	RN002348/01-010212	42-28-398-10	General biological properties; typical of F. tularensis subsp. holarctica strains; concentration of live immunogenic bacterial colonies (SR-type) ≥80%; agglutination with diagnostic tularemia antiserum & specific FITC-immunoglobulins; ‘residual virulence’ (LD50 for albino mice 158-500 CFU); storage stability	Guinea pigs and guinea pigs	80	10
Cholera	PR #1846-06	Under review	General biological properties; typical of V. cholerae O1; s-type of bacterial colonies; virulence for each of production strains of V. cholerae O1; presence of ctx A & B in the production strain V. cholerae 569B; presence of O-antigen in the production strain V. cholerae M-41	Rabbits and albino mice	Not applicable	3
Glanders	PR # 1901-07	Under review	Sterility; non-toxic for albino mice (0.2 mL); pyrogen-free for rabbits (1 mL injected to aural vein); non-infectious for guinea pigs during 30 days after s.c. injection 0.5 mL	Guinea pigs and albino mice and guinea pigs (≤70% animals survived during 15 days after challenge with 1 mL of virulent strain B. mallei C-5)	ND	ND
Brucellosis	FSP R N003612/01-010212	42-28-396-11	General biological properties; typical of Brucella; agglutination with diagnostic brucella antiserum; absence of bacteriophage; no colony dissociation; ‘residual virulence’ for albino mice 5×10^2–5×10^5 CFU	Albino mice and guinea pigs (survival after challenge with the wild-type strain B. melitensis 565 ≥70%)	60	10

Abbreviations: FITC, fluorescein isothiocyanate; LD50, lethal dasage 50%; ND, not applicable.