HeberNasvac: Cuban scientists' achievement against hepatitis B

Eight years after the approval of the Cuban vaccine HeberNasvac, to treat chronic patients infected with hepatitis B virus, the Center for Genetic Engineering and Biotechnology (CIGB by its Spanish acronym) continues its research with the immunogen in Japan and Bangladesh, where it has obtained encouraging results.

In an interview with the Cuban News Agency, PhD in Biological Sciences Gerardo Guillen Nieto, director of Biomedical Research of the CIGB, pointed out that the drug is still very innovative, since it is the only vaccine against a chronic infectious disease and the only therapeutic vaccine administered nasally.



He commented that after obtaining the sanitary registration in Cuba, in collaboration with the French company Abivax, they carried out studies in South Korea, New Zealand, Singapore, Australia, Philippines, Taiwan, Thailand and Hong Kong; with the approval of the regulatory authorities of those nations, an experience that increased the evidence of the vaccine's safety.

The member of the BioCubaFarma-Ministry of Public Health ( MINSAP by its Spanish acronym) Innovation Committee and of the Science Advisory Group of MINSAP pointed out that in the clinical studies, HeberNasvac reduced the amount of virus in blood to less than 10,000 particles per milliliter in about 80 % of the patients.

The expert explained that in these cases they are still infected with the virus, but by having a low level of viral multiplication, the risk of suffering fibrosis and progressing to cirrhosis or liver cancer is significantly reduced. Furthermore, we have seen that 80 % of the individuals, even after five years of treatment, keep the viral load under control; and in 50 % of them, this load is not detectable.

Based on the research conducted in Bangladesh, where patients report a more active disease -they have a marker called E-positive antigen, which is more frequent in Southeast Asia-, antibodies against that antigen were achieved in about 60 % of them, he said.

In that country, Cuban scientists in collaboration with local gastroenterologists are studying the effects of HeberNasvac in patients with hepatitis B who initially were treated with antivirals and their administration was stopped in order to apply the vaccine. The patients of the efficacy study (phase III) carried out in that country, which allowed the sanitary registration of HeberNasvac in Cuba, have also been followed up.

The director of Biomedical Research of the CIGB mentioned that the second clinical study carried out in Japan is also underway in that country, which aims to include more than 300 volunteers; of which more than 100 have already been included, in an investigation that seeks to determine the efficacy of the vaccine in a new formulation and in different clinical scenarios, including patients who did not respond to the antiviral treatment and patients for whom no treatment is currently available.

It is important to be able to treat these people. Evidence from a preliminary (phase I) study already completed indicates that HeberNasvac is effective and its results have been recognized for two consecutive years as one of the most important in hepatitis B therapy presented at the annual meeting of the American Society of Liver Diseases, the researcher noted.

How does the vaccine work?

It has been demonstrated that HeberNasvac, an immunogen that in the scheme currently registered in Cuba is administered by the nasal route combined with the subcutaneous route, is effective against a disease that has little effective treatments, due to the fact that the antivirals currently used are not capable of achieving the functional cure; that is to say, that people develop antibodies against the virus and eliminate the circulation in blood of the virus antigen known as surface antigen, so the risk of developing fibrosis in the liver, cirrhosis and liver cancer is maintained in time.

The PhD in Biological Sciences and member of the Academy of Sciences of Cuba, explained that chronic hepatitis B evolves in the long term, most infected people do not even know they are infected or they discover it when it is a little late, and the fact is that -as it happens with cancer or AIDS- the immune system does not defend itself, hence the vaccine uses the nasal route to break that tolerance and induce an immune response.

Other advantages of the immunogen are related to safety and administration time. The vaccine is very safe, with few adverse reactions, and its treatment schedule of around five months is shorter compared to interferon, which is applied for a year and causes adverse reactions as well as antivirals, which is the other existing treatment, in the latter case it must be administered for life, he explained.

Hepatitis B is not a health problem in Cuba.

In Cuba, the incidence of hepatitis B has decreased, so it is no longer a health problem, and the country is working in line with the World Health Organization's initiative to eliminate it by 2030.

According to MINSAP figures in relation to acute hepatitis B during 2021, 35 cases were reported in the country compared to 58 in 2020, for a rate of 0.46 per 100 thousand inhabitants, which decreased by 39.7% compared to the previous year. While of chronic hepatitis B, 21 cases were diagnosed in 2021 compared to 73 in the previous year, for a rate of 0.28, and decreased reporting by 71.3%.

The CIGB was influential in achieving these results when it developed the Heberbiovac HB preventive vaccine in 1991, which made it possible that as early as the year 2000 there were no reports of the disease in children from zero to five years of age and by 2005 it had been eliminated in infants and adolescents up to 15 years of age.

Guillen Nieto assured that we have the advantage of broad immunization coverage with this preventive vaccine and the Heberpenta-L pentavalent vaccine developed by the CIGB in 2009, which includes the preventive vaccine against hepatitis B, which is why most people are protected against the virus and the incidence of liver cancer is very low.

In addition, the technological platform used for Heberbiovac HB made it possible to achieve the HeberNasvac vaccine and the vaccine candidate Mambisa against COVID-19; the latter has among its components the hepatitis B virus nucleocapsid antigen, one of the components of HeberNasvac, as an immune response enhancer.