Ebola vaccine

There are limited amount of data (less than 300 pregnancy outcomes) from the use of ebola vaccine in pregnant women, or women who became pregnant after receiving the vaccine. The safety of ebola vaccine has not been established in pregnant women.

As there are limitations to available data, including the small number of cases, caution should be exercised in drawing conclusions. Lack of reliable data on background rates of pregnancy and neonatal outcomes in the affected regions also makes a contextual assessment of the data challenging.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

As a precautionary measure, it is preferable to avoid the use of ebola vaccine during pregnancy. Nevertheless considering the severity of EVD, vaccination should not be withheld when there is a clear risk of exposure to Ebola infection.

Pregnancy should be avoided for 2 months following vaccination. Women of child-bearing potential should use an effective contraceptive method.

It is unknown whether the vaccine virus is secreted in human milk.

A risk to the newborns/infants from breast-feeding by vaccinated mothers cannot be excluded.

Evaluation of the vaccine virus in animal milk has not been conducted. When ebola vaccine is administered to female rats, antibodies against the vaccine virus were detected in offspring, likely due to acquisition of maternal antibodies via placental transfer during gestation and via lactation.

A decision must be made whether to discontinue breast-feeding or to abstain from ebola vaccine taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. In certain circumstances, where alternatives to breast-feeding are limited, the immediate need and health benefits to the infant should be taken into consideration and balanced with the mother’s need for ebola vaccine. Both may present compelling needs that should be considered before vaccination of the mother.

Fertility

There are no data on fertility effects in humans.

Animal studies in female rats do not indicate harmful effects.

No studies on the effects of ebola vaccine on the ability to drive and use machines have been performed.

Ebola vaccine has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

Anaphylaxis was reported very rarely (0.006%) in clinical trials.

The most common injection-site adverse reactions were injection-site pain (70.3%), swelling (16.7%) and erythema (13.7%).

The most common systemic adverse reactions reported following vaccination with ebola vaccine were headache (36.9%), pyrexia (34.3%), myalgia (32.5%), fatigue (18.5%), arthralgia (17.1%), nausea (8.0%), chills (6.3%), arthritis (3.7%), rash (3.6%), hyperhidrosis (3.2%), and abdominal pain (1.4%). In general, these reactions were reported within 7 days after vaccination, were mild to moderate in intensity, and had short duration (less than 1 week).

Tabulated list of adverse reactions

Frequencies are reported as: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Tabulated summary of adverse reactions considered related to vaccination:

^§ See description of selected adverse reactions.

Description of selected adverse reactions

Arthralgia and arthritis

Arthralgia was generally reported in the first few days following vaccination, was mild to moderate in intensity, and resolved within one week after onset. Arthritis (arthritis, joint effusion, joint swelling, osteoarthritis, monoarthritis or polyarthritis) was generally reported within the first few weeks following vaccination. In clinical trials with reports of arthritis, the median onsets were between 10 and 12 days (range from 0 to 25 days). Arthritis has been reported by subjects in clinical trials at a frequency that ranged from 0% in several protocols to 23.5% in one Phase 1 study. The majority of arthritis reactions were mild to moderate in severity. The median duration of arthritis across clinical trials in which arthritis was reported ranged from 2 days to 81.5 days (including duration of recurrent arthritis) with a maximum of 330 days. The reasons for differences in arthritis reporting across trials are not known but may be due to differences in study populations or outcome reporting. In the Phase 1 study with the highest rate of arthritis, 6 of 24 patients (25%) who reported arthritis after vaccination had persistent joint symptoms two years after vaccination. In a small number of subjects, the vaccine virus was recovered from joint effusion samples, suggestive ofa virally-mediated process postvaccination.

Rash

Rash was characterised in a variety of ways including generalised rash (2.3%), vesicular rash (0.5%), dermatitis (0.3%), or cutaneous vasculitis (0.01%) in clinical trials. In different trials, rash was reported with median onsets of 7.5 to 10.5 days (range from 0 to 47 days). The median durations reported were between 6 to 18 days. In 6 out of 18 subjects tested, the vaccine virus was detected in rashes (described as dermatitis, vesicles or cutaneous vasculitis lesions) suggesting a virally mediated process post-vaccination.

Transient decrease in white blood cells

Transient decreases in counts of lymphocytes, neutrophils and total white blood cells in the first 3 days following vaccination have been observed very commonly in Phase ½ studies; these events generally resolved after the first week post-vaccination. No adverse events of infections were observed in Phase ½ trials.

Paediatric population

Across the Phase 1 through Phase 3 trials, 234 children and adolescents 6 to 17 years of age received a dose of ebola vaccine.

The safety profile of ebola vaccine in children and adolescents 6 to17 years of age was generally similar to that observed in adults.