Evolution of biotechnology: the future of vaccine design

Dr. Sherry Layton, Ph.D., Director of Biotechnology Vetanco / BVSience was responsible for the conference “Evolution of Biotechnology: The Future of Vaccine Design” during the LPN Congress 2018.

The development of new vaccines for effectively controlling pathogens and infection in the host represents a critical area of research and development to reduce the impact of diseases in animals destined for human consumption, even more with the increasing restrictions in the prophylactic and therapeutic use of antibiotics.

Recent advances in biotechnology have dramatically increased the potential for scientific innovations, allowing the incorporation of new technologies in the form of alternative pathogen control strategies.

One of the newest biotechnology available is a new vaccine platform that incorporates the subunit/epitope sequence, common to all serotypes/serovars of a specific family of pathogens (broad spectrum), into an inactivated form of a vaccine platform administered orally, inducing protection against infection and disease by stimulating mucosal immunity.

The mucous membranes are the main route of entry for pathogens and include the membranes of the nasal, respiratory, gastrointestinal, and genitourinary tracts, as well as the ocular conjunctiva, inner ear, and ducts of all exocrine glands. They occupy more than 400 m2 in humans – compared to just 2 m2 of skin – and act as the first line of defense against infection at entry points for various pathogens (Ogra et al., 2001).

Gastrointestinal system

The gastrointestinal system is the largest lymphatic organ in the body, estimated to house 70-80% of immunoglobulin-producing cells (Kaul, 1999).

80% of the activated B lymphocytes in the body are located in the mucosal tissues (Brandtzaeg et al., 1989). In fact, 95% of the pathogens that enter do so through a mucosa; the only way to contract a disease by a route other than the mucosa is through blood-feeding vectors or damaged epithelial surfaces.

Despite this critical role, only a few vaccines specifically target this part of the immune system, despite strong evidence that a robust mucosal response can prevent systemic infections (Ogra et al., 2001).

To date, conventional vaccine studies have focused on stimulating the systemic immune system to generate immunity that neutralizes/prevents organisms once they have colonized the organism, multiplied, and passed into the systemic environment.

However, inhibiting the colonization and replication of pathogens directly at the gateway has been considered a secondary aspect, and not enough attention has been paid to it.

Evidence indicates that mucosal vaccination can induce systemic and local immunity, while systemic immunization often fails to stimulate strong mucosal immunity (Valosky et al., 2005).

Furthermore, the concept of a common mucosal immune system predicts that induction of immunity at one mucosal surface, such as the gut, can induce immunity at another mucosal surface, such as the lung (Cerkinksky et al., 1995), providing an essential connection to transfer immunity across mucous membranes.

Mucosal immunity could be the key to fighting complex infections where systemic and local immunity is necessary to prevent the spreading and transmitting of infectious diseases within a herd or flock.

Disease control and vaccination strategies

Discussion of disease control and vaccination strategies should not stop only at localization change, where the primary immune response occurs at the initial point of host-pathogen interaction.

The perception of what is considered an infectious disease must also undergo a paradigm shift. The clearest example of this mindset shift is the idea of what exactly commensal bacteria constitute the mucosal microbiome.

Can they be classified as bacteria that do not actually harm the host? Is there an absence of clinical manifestations caused by true mucosal pathogens (pathobionts)?

Perhaps the resident bacteria are responding to a failure of the mucosal immune system? A complete answer would be a combination of the three previous options, as well as an additional fourth component since there are bacteria that are really beneficial for the host’s health status.

Development of new technologies

An additional question that deserves in-depth reflection when developing new technologies as a disease control tool is: are animals/birds becoming asymptomatic carriers with modified immune responses that favor the survival of pathogens to the detriment of autobionts? that regulate and maintain the host’s immune system healthy and stable (Ivanov, 2013)?

New vaccine technologies created to control diseases must focus on stimulating an immune response that is more beneficial for the host than for the pathogen, even if this implies a reprogramming or a change in the way the host responds to a particular pathogen at a general and cellular level.

Traditional vaccination, either through inactivated vaccines or live attenuated vaccines, has an additional shortcoming that needs to be addressed by new alternative technologies.

Historically, traditional vaccines have been limited in scope, with little or no cross-protection between genetically related pathogen serotypes.

Consequently, a single vaccine strain has been used to vaccinate against one serotype/serovar in host species. For significant advances in disease prevention to occur, the focus must shift to the more progressive and inclusive “One Health” concept, in which vaccination targets families of pathogens across multiple host species.

One possible solution is using a single conserved protective protein or a subunit, which confers protection against all serotypes/serovars of a specific family of pathogens (bacteria, viruses, and protozoa) in multiple host species carried by an inert vector.

Vaccine vectors

Several vaccine vectors have emerged, all with relative advantages and limitations, depending on the proposed application.

Bacteria, viruses, and plants represent three potential orally administrable vector systems for inducing mucosal immunity and protective immune response.

Bacillus family bacteria, specifically Bacillus subtilis, have shown a promising alternative to the use of pathogenic bacteria as an orally administered vaccine vector since they have an intrinsic adjuvant activity that enhances the stimulation of the host’s specific mucosal immunity against bacteria-vectorized subunits.

In addition, Bacillus subtilis has probiotic properties, stimulating and enhancing gastrointestinal integrity, which is necessary for a healthy state of the animal/bird. Likewise, this vaccine strategy with a common unit carried by an inert vector could limit the vaccine reactions produced when the complete cell of the pathogen (inactivated, attenuated, or as a vector) is presented to the host.

The final goal of intensive animal production is to identify and eliminate pathogens before they can cause disease. Today more than ever, multifactorial solutions to disease must be addressed, not only focusing on treating the effects of the disease but, more importantly, on preventing disease.

Thanks to biotechnology, we can now better understand what constitutes a disease, how the pathogen and the host influence immune competition, and the complex dynamics associated with the host-pathogen interaction.

All the essential information and discoveries will allow researchers to move forward with biotechnology, and new vaccination technologies, integrating the concept of “One Health” as an alternative disease control strategy.