We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus’ entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.

KEYWORDS Immunity, innate; toll-like-receptors; SARS-CoV-2; COVID-19; respiratory tract infections; Cuba

Hepatitis B causes liver failure, cirrhosis and cancer. It has an estimated global prevalence of 6%, and 700,000 to 1 million persons die every year of hepatitis B-related causes. In 1989, hepatitis B incidence in Cuba was 14.9 per 100,000 population. To control infection, the Genetic Engineering and Biotechnology Center and the Ministry of Public Health, both in Havana, collaborated on a joint project that first produced natural interferon and recombinant interferon alpha-2b, and later a polyethylene glycol-conjugated interferon. As part of the Cuban biotechnology development strategy, the project produced a vaccine against hepatitis B in 1985. At that time, hepatitis B vaccines available elsewhere in the world were costly and inaccessible to Cubans due to the US economic and trade embargo. The Heberbiovac HB preventive vaccine was approved by the Cuban regulatory authority and added to the Cuban newborn vaccination program in 1992 after phase 1–3 clinical trials demonstrated its safety and immunogenicity. From 2001 to 2003, PAHO/WHO qualified and requalified the vaccine four times. When associated with other antigens or molecules, Heberbiovac HB provides a common platform of virus-like particles that can be used in different ways, such as in the pentavalent vaccine containing Bordetella pertussis and Haemophilus influenzae type b antigens and tetanus and diptheria toxoids.

Thanks to this vaccine, annual incidence of acute hepatitis in Cuba has dropped from more than 2000 cases to fewer than 100, and no infections in children aged 0–15 years have been reported since 2007. It is now used in more than 30 countries, providing protective, long-lasting antibody levels with no reports of serious adverse events.

Yet, hepatitis B cannot be eliminated until there are no chronic patients. The comprehensive hepatitis B control project therefore included development of a therapeutic vaccine based on Heberbiovac HB. Using its platform, researchers designed an innovative version of the vaccine that was the precursor of a therapeutic nasal/subcutaneous vaccine for chronic hepatitis B, HeberNasvac. This precursor vaccine, which combines Heberbiovac HB with a recombinant antigen from the virus nucleocapsid (rHBcAg), was patented and licensed in 2015 by the Cuban regulatory authority. This article provides an overview of the progress-to-date on the development of this therapeutic vaccine, including clinical trials (some completed and others ongoing) to determine safety, efficacy and therapeutic benefits.

KEYWORDS Hepatitis B, vaccines, recombinant DNA, clinical trials, Cuba