Anthrax vaccine: who is it indicated for?

Anthrax is an acute bacterial infection caused by the spore-forming bacterium Bacillus anthracis. The greatest threat comes from inhalation, where spores are inhaled and, without early treatment, can rapidly worsen the condition. Vaccination is intended to protect individuals at occupational risk and for emergency prophylaxis following potential exposure to the bacteria. [1]

The infection manifests itself through cutaneous, inhalation, gastrointestinal, and injection routes. Severity is associated with the production of toxins, including a protective antigen, lethal factors, and edema factors. Modern vaccines target the formation of antibodies to the protective antigen, a key component of the toxin. [2]

The risk to the general population is low, but it can be significant for certain professions. Therefore, vaccines are administered on a targeted basis: pre-exposure to laboratory workers, veterinary and tannery workers, and certain military units, and post-exposure in combination with antibacterial drugs. [3]

Mass immunization of the population is not being carried out. However, the availability of effective post-exposure prophylaxis regimens can significantly reduce the likelihood of developing the disease in exposed individuals. [4]

Types of human anthrax vaccines and how they work

In clinical practice, vaccines obtained from the culture filtrate of Bacillus anthracis strains with subsequent adsorption of antigens onto aluminum adjuvants are used. The primary immune target is a protective antigen, to which toxin-neutralizing antibodies are formed, blocking the action of toxins. [5]

The classic BioThrax vaccine is intended for routine protection and post-exposure prophylaxis in a three-dose regimen alongside antibacterial therapy. The vaccine is administered subcutaneously for emergency regimens and intramuscularly for routine protection, due to varying tolerability profiles. [6]

The new adjuvanted two-dose vaccine Cyfendus is indicated for post-exposure prophylaxis in adults aged 18–65 years and is administered intramuscularly twice, 14 days apart. Efficacy has been validated using the Animal Rule, comparing functional antibody levels and survival in animal models with the human immune response. [7]

A number of countries use national vaccines and schedules that differ in the number of doses and intervals. The choice is guided by local regulations and epidemiology, but the general principles remain the same: early initiation of post-exposure prophylaxis, combination with antibacterial drugs, and, in the case of routine protection, titer maintenance through revaccination in those still at risk. [8]

Table 1. Major human anthrax vaccines

Name	Type and composition	Indications	Age	Route of administration	Regulatory guidelines
BioThrax	Adsorbed antigens of the protective antigen	Routine protection in risk groups, post-exposure prophylaxis	18-65	Intramuscularly for planned protection, subcutaneously for emergency treatment	US Instructions and MMWR [9]
Cyfendus	Adsorbed antigens plus CpG adjuvant	Post-exposure prophylaxis in combination with antibacterial drugs	18-65	Intramuscularly	US Registration and FDA Materials [10]
National variants	Similar approaches to the protective antigen	According to local indications	According to local indications	According to local indications	Government Agency Guidelines [11]

Who is eligible for vaccination: risk groups

Routine protection is recommended for laboratory staff handling Bacillus anthracis, veterinary specialists, and workers exposed to raw hides, wool, and other animal products from endemic regions, as well as certain categories of military personnel and emergency response teams. The decision is made based on an assessment of the likelihood of exposure. [12]

Post-exposure prophylaxis is indicated for all individuals after probable or confirmed contact with spores. The earlier the regimen is started, the higher the likelihood of preventing the disease. This includes immediate administration of antibacterial drugs and vaccination at approved intervals. [13]

For the population without occupational risk, routine vaccination is not required, as the likelihood of exposure is extremely low. Exceptions include biological threat situations and local outbreaks, where emergency prevention protocols are applied. [14]

In European countries and the UK, the approach is similar: vaccination is carried out specifically for individuals at risk, taking into account national regulations and drug availability. [15]

Table 2. Who is eligible for the anthrax vaccine?

Category	Examples of situations	Type of protection	Note
Laboratory workers	Bacillus anthracis culture	Planned	Series and revaccination if risk persists [16]
Professional contacts with raw materials	Skins, wool, bones from endemic regions	Planned	According to the risk assessment of the employer and the physician [17]
Military personnel and emergency teams	Duties and operations in risk zones	Planned	According to departmental regulations [18]
Any persons after possible contact	Suspected spore inhalation	Post-exposure	Immediate antibiotics plus vaccination [19]

Planned protection schemes for risk groups

For routine protection with the BioThrax vaccine, a three-dose primary series is used: at baseline, 1 month, and 6 months, followed by boosters at 12 and 18 months, and then annually if the risk continues. The intramuscular route is better tolerated than the subcutaneous route, with comparable immune efficacy. [20]

If the primary series is interrupted, it is resumed without starting from scratch, observing minimum intervals. If the risk temporarily disappears, further booster vaccinations can be postponed until the risk returns, based on local guidelines and an assessment of occupational exposure. [21]

For high-risk workers, dates, lots, and sites of administration should be recorded, and the timeliness of booster doses should be monitored. This practice improves compliance and provides documentation of vaccination. [22]

Intramuscular administration reduces the incidence of local reactions such as pain, redness and induration, which is especially important for long-term programs in professionals. [23]

Table 3. Planned BioThrax protection in risk groups

Stage	Time	Route of administration	Comment
Dose 1	Day 0	Intramuscularly	Beginning of the series [24]
Dose 2	1 month	Intramuscularly	Formation of the primary response [25]
Dose 3	6 months	Intramuscularly	Completion of the primary series [26]
Revaccinations	12 and 18 months	Intramuscularly	Maintenance of antibody titers [27]
Further	Annually at risk	Intramuscularly	While the exposure remains [28]

Post-exposure prophylaxis: what to do after possible infection

Step one is the immediate initiation of antibacterial drugs with proven activity against the pathogen. Fluoroquinolones or tetracyclines are typically used in standard doses. The choice of specific drug and duration depend on vaccination status, age, and immune status. [29]

Step two is the start of vaccination. For BioThrax, the emergency regimen consists of three doses administered at 0, 2, and 4 weeks, along with an ongoing course of antibacterial drugs. For Cyfendus, adults aged 18-65 years are administered two intramuscular doses 14 days apart, in combination with the recommended antibacterial therapy. [30]

For immunocompetent adults receiving BioThrax on a regular schedule, the course of antibacterial drugs can be shortened to 42 days from the start of treatment or 14 days after the last dose of vaccine, whichever is longer. For pregnant women, children, the elderly, and immunocompromised individuals, the full course of up to 60 days is maintained. [31]

Decisions to use antitoxin are made based on signs of a systemic process and severe progression. In uncomplicated post-exposure prophylaxis, timely administration of antibacterial drugs and a vaccine according to the approved regimen play a key role. [32]

Table 4. Emergency schemes after contact

Scheme	Vaccine	Intervals	Accompanying measures
Three-dose	BioThrax	Day 0, Week 2, Week 4	Antibacterial drugs for up to 42-60 days according to indications [33]
Two-dose	Cyfendus	Day 0 and Day 14	Concomitant antibacterial therapy is mandatory according to the protocol [34]

Efficacy and immune response: what counts as protection

Evaluation of the efficacy of modern vaccines is based on the level of functional toxin-neutralizing antibodies to the protective antigen. For Cyfendus, antibody levels in humans were compared with thresholds associated with survival in animal models, which is consistent with the regulatory approach when efficacy studies in humans are not feasible. [35]

With Cyfendus, the peak immune response is observed approximately 4 weeks after the second dose, which is within the early protection window when antibacterial therapy is initiated correctly. This is especially important in cases of inhalation exposure, when the rate of immune response is critical. [36]

For BioThrax, a three-dose series for routine protection produces a robust response that is maintained by booster doses in those still at risk. For emergency use, three doses combined with antibacterial agents reduce the likelihood of infection after exposure. [37]

Data on the combined use of Cyfendus with ciprofloxacin and doxycycline show no clinically significant effect on the pharmacokinetics of the drugs or on the immune response of the vaccine, confirming compatibility within the framework of post-exposure prophylaxis. [38]

Table 5. Immune response and timing

Parameter	BioThrax	Cyfendus
Target antigen	Protective antigen	Protective antigen plus CpG adjuvant [39]
Formation of the primary response	After completing three doses	After the second dose by week 4 [40]
Maintenance	Revaccinations at risk	Not suitable for routine protection.
Compatibility with antibacterial drugs	Standard	No significant interaction with ciprofloxacin and doxycycline was observed [41]

Safety and adverse reactions

The most common reactions are pain, redness, and induration at the injection site, short-term fever, weakness, and muscle pain. The intramuscular route of BioThrax is associated with a lower incidence of local reactions compared to subcutaneous administration. Severe reactions are extremely rare. [42]

For Cyfendus, the frequency of local reactions is comparable to that expected for adjuvanted vaccines. According to clinical trials, the most common reactions were soreness and pain at the injection site, as well as muscle pain, usually mild to moderate in severity and self-limiting. No new safety signals were identified. [43]

Immediate allergic reactions are rare but require standard preparedness at the vaccination site. Reports of serious adverse events are isolated and do not alter the benefit-risk balance in individuals with indications. [44]

Factors such as gender and body weight may influence the local reaction profile, but this is usually of little clinical significance. The physician informs the patient of typical post-injection sensations and signs that indicate the need to seek medical attention. [45]

Table 6. Adverse reactions and their frequency

Reaction	Description	Frequency Notes
Soreness and pain	At the injection site	Often, briefly, self-limiting [46]
Redness and hardening	Local manifestations	More common with subcutaneous administration of BioThrax [47]
Fever and weakness	Systemic manifestations	Usually mild [48]
Allergic reactions	Itching, urticaria, anaphylaxis	Very rare, standard willingness to help [49]

Special groups: pregnancy, children, elderly, immunocompromised

For planned protection during pregnancy, vaccination is postponed if possible, except in situations where the risk of exposure is significant and the benefits outweigh the potential risks. After possible exposure, the decision is made on an individual basis, with priority given to antibacterial agents with a known safety profile. [50]

In children, the use of vaccines is decided by health authorities in emergency situations. In routine practice, routine protection is not provided to children; the emphasis is on contact prevention and early initiation of antibacterial drugs if exposure is suspected. [51]

In elderly individuals and those with immunodeficiencies, the duration of the course of antibacterial drugs after contact is usually not shortened and is up to 60 days, since the formation of a full-fledged immune response may be reduced or slowed down. [52]

When breastfeeding, decisions are made based on the risk of exposure and the need for post-exposure prophylaxis. Published guidelines allow for prophylaxis and treatment, taking into account drug safety and the timeliness of intervention. [53]

Table 7. Special groups and key considerations

Group	Planned protection	After contact
Pregnancy	Postpone if possible	Individual decision, priority of antibacterial drugs [54]
Children	Not used routinely	According to decisions of health authorities in emergency situations [55]
Elderly	Conventional approaches	A full course of antibacterial drugs for up to 60 days [56]
Immunodeficiency	Conventional approaches	A full course of antibacterial drugs for up to 60 days [57]

Contraindications and precautions

An absolute contraindication is a severe allergic reaction to a previous dose or vaccine components. Relative restrictions include acute febrile conditions: vaccination is postponed until recovery. Decisions regarding individuals with chronic medical conditions are made on an individual basis, based on the risk assessment. [58]

For routine protection, assess occupational risk, allergy history, pregnancy, and potential drug interactions. Provide observation for the prescribed period after injection and instruct the patient on signs requiring medical attention. [59]

For post-exposure prophylaxis, the "benefit outweighs the risk" principle often dictates rapid action. If there are contraindications to a specific vaccine, alternative measures are considered in combination with antibacterial drugs and observation. [60]

Mass post-exposure vaccination programs require strict documentation, temperature control, and routing of people to ensure intervals are maintained. This is critical to effectiveness. [61]

Table 8. Contraindications and precautions

Paragraph	Content
Absolute contraindication	Severe allergic reaction to a previous dose or components of the vaccine [62]
Relative restrictions	Acute febrile conditions, decision to postpone until recovery [63]
Special circumstances	Rapid decisions when dealing with safety and efficiency as a priority [64]

Introduction and storage practice: how to do it right

For routine protection, the intramuscular route is preferred due to its better tolerability. For emergency regimens with BioThrax, the subcutaneous route can be used in accordance with the instructions. If necessary, health authorities allow route adaptations to avoid delaying the start of prophylaxis. [65]

Storage is carried out at a temperature of 2 to 8 degrees Celsius, maintaining a cold chain. The vaccine is not frozen and is protected from light. Expiration dates and specifications for multi-dose vials are specified in the manufacturer's instructions. [66]

If a dose is missed, it should be administered as soon as possible, maintaining the general sequence. There is no need to restart the series unless there is a long, unexplained break. The physician will adjust the schedule to accommodate the minimum intervals. [67]

The combination of Cyfendus with ciprofloxacin or doxycycline does not reduce the immune response and does not clinically significantly change the pharmacokinetics of these drugs, making co-administration justified as part of post-exposure prophylaxis. [68]

Table 9. Introduction and storage: key points

Topic	Recommendation
The preferred route for planned protection	Intramuscularly for better tolerability [69]
BioThrax Emergency Schemes	Subcutaneous administration is possible according to the instructions [70]
Temperature conditions	From 2 to 8 degrees, without freezing [71]
Compatibility with antibacterial drugs	Acceptable and clinically justified for ciprofloxacin and doxycycline [72]

Frequently asked questions

Does everyone need vaccination after exposure to the spores?
Yes, in cases of probable or confirmed exposure, post-exposure prophylaxis is indicated: immediate antibacterial drugs and a vaccine according to the approved regimen. Vaccine choice depends on age and availability. [73]

Is it possible to shorten the duration of antibacterial treatment?
For immunocompetent adults taking BioThrax as scheduled without interruption, the duration may be reduced to 42 days. For the elderly, pregnant women, children, and those with immunodeficiencies, the duration is maintained at 60 days. The decision is made by the physician based on protocol. [74]

How quickly does protection develop with Cyfendus?
Four weeks after the second dose, functional antibody levels are achieved that correspond to the desired early protection profile when antibacterial drugs are prescribed correctly. [75]

What is the difference between routine protection and post-exposure prophylaxis?
Routine protection involves a three-dose series and booster doses for individuals at constant risk. Post-exposure prophylaxis involves emergency regimens following exposure, including mandatory administration of antibacterial medications. [76]

When is antitoxin required?
Antitoxin is considered in cases of systemic symptoms and severe forms, along with antibacterial drugs and supportive therapy. It is not included in prophylactic regimens without signs of illness. [77]