Evaluation of the sublingual route of immunisation for the induction of mucosal and systemic immune responses to polysaccharide-protein conjugate vaccines


The aim of this project is to investigate whether administering a vaccine under the tongue (i.e. sublingually) is more effective than injecting the vaccine, with the goal of preventing infections such as those caused by group A and group B streptococci bacteria. Infections caused by these bacteria result in significant illness and mortality burden, especially in low and middle income countries, and there are no vaccines against these streptococci. A new type of vaccine against group B streptococcus is currently being developed by the industrial partner, and this vaccine will be used to test the aim.   

The sublingual route has been selected for its advantages over the injection. Injected vaccines do not always elicit immune responses at the body’s surfaces where group A and group B streptococci enter, infect or are transmitted to others, such as the nose, mouth, intestine, lungs and vagina. In contrast, when vaccines are administered sublingually, immune responses are generated at these sites and in the blood. Immunity at all these places (elicited by sublingual vaccine administration) is therefore more likely to prevent infection by group A and group B streptococci. In addition, the sublingual route avoids the needle and associated problems. In this project, we will administer the vaccine sublingually to experimental animals. Control animals will receive the vaccine by injection. Immune responses in the blood, mouth, nose, intestine and vagina will be measured. The results will establish the potential superiority of the sublingual route for administration of the type of vaccine used.

Project outcomes

Group B Streptococcus (GBS) is a bacterium that is commonly present in adults, in the gut and vagina, and usually does not cause any harm.  Occasionally, GBS is transmitted from the mother to the baby during birth, causing meningitis, septicaemia and pneumonia in the first week of life.  

Despite the strategies currently in place to prevent GBS infection in newborns i.e. antibiotics given to the mother, on average in the UK, 2 babies a day develop a GBS infection, and as a result, one baby dies every week, while another baby survives with long-term disability in the UK.  This shows the urgent need for additional strategies, such as vaccinating pregnant women (as vaccinating newborns is not feasible).  However, there are no commercially-available vaccines yet.

We have investigated the possibility of giving pregnant women a vaccine under the tongue i.e. sublingually, so that there would be immunity in the vagina, which would in turn prevent transmission of GBS bacteria from the mother to the baby during vaginal birth.  The sublingual route was chosen as it has been shown to generate immunity in the vagina for other vaccines and it is pain-free, practical, cheap and acceptable to patients.  It is also needle-free, thus it does not require injection by trained professionals and eliminates needle-related problems, such as disease transmission from accidental needle-stick injuries or from reuse of contaminated needles.

Our experiments in the laboratory have shown that giving a GBS vaccine sublingually in the mouse (an animal model) did indeed generate immunity in the vagina.  In addition, immunity was also generated in the mouth, in the gut and in the blood.  Statistically, the sublingual route was more effective than the injection route at generating immunity in the vagina, mouth and gut.  This shows that in order to prevent transmission of the GBS from the mother to the baby during vaginal birth, and afterwards once the baby is born, giving a vaccine sublingually should be the preferred option compared to the injection.  In addition, the sublingual route was statistically as effective as the injection route at generating immunity in the blood.  This means that the sublingual route can enable immunity generated by the mother during pregnancy to pass to the foetus via the placenta, which would also protect the newborn against developing a GBS infection.    

Subsequent experiments with sublingual vaccination showed that it was possible to reduce the dose of the vaccine five-fold without affecting the immunity in the vagina, mouth, gut and blood.  This would significantly reduce the cost of the vaccine.  Other experiments have shown that it is also possible to reduce or replace a toxin-based adjuvant (vaccine helper) with a safer alternative without affecting the immunity greatly.  

Sudaxshina Murdan
Dr Sudaxshina Murdan
Associate Professor
School of Pharmacy, University College London (UK)

Dr Fatme Mawas, National Institute for Biological Standards and Control, MHRA (UK)

Dr Seanette Wilson, The Biovac Institute (Biovac) (South Africa)