Development of vaccines and vaccines for pandemic threats (in particular for COVID19)

ABSTRACT

Vaccines, currently used for prophylactic purposes, prevent more than three million deaths every year from diseases like diphtheria, pertussis, tetanus, poliomyelitis, measles and influenza. The general six stages of the development of a new vaccine are i) Exploratory stage;ii) Pre-clinical stage;iii) Clinical development;iv) Regulatory review and approval;v) Manufacturing;vi) Quality control. Clinical development is a three/four-phase process. During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety. Many vaccines undergo Phase IV formal, ongoing studies after the vaccine is approved and licensed. Phase IV studies, also referred to as postmarketing surveillance studies (PMS). These processes are very similar to drug developments. However, there are several differences compared to drug development, namely i) unlike drugs, which are given to patients, vaccines are received by healthy individuals, thus the safety margin should be very high;ii) as vaccines have to be stored under refrigeration, there are always logistical challenges during clinical trials;iii) Adjuvants are incorporated into vaccine formulations to modulate and improve the immune response (antigen/adjuvant formulation are important aspects of clinical development);iv) The immune response primarily measured during early stages of vaccine development (Phase I/II) should evaluate Humoral/ cell-mediated/ cross-reactive antibodies or immune complexes/ immune landscape. A challenge in responding to pandemic diseases is that vaccines may not exist for them. For newly emerging threats without licensed vaccines, such as SARS, MERS, Marburg virus, Nipah virus, SARS CoV-2 and the like, the time required to develop and produce a safe, effective vaccine is unknown and would depend on the nature of the threat and the state of current vaccine research for that threat. In almost all cases, several months would be needed to respond with the first doses of vaccines. Unfortunately, six month later than WHO declared the public health emergency of international concern (27/01/2020) there are five important questions, essential for vaccine development that remain open for scientists, namely 1) Why do people respond so differently to infection? 2)Has the virus developed any worrying mutations? 3)How well will a vaccine work? 4)Can we develop immunity and if so, how long does it last? 5)What is the origin of the virus? Until a safe, effective vaccine was ready, other public health and medical measures (social distancing, quarantine, and aspecific medications) would need to be employed to try to limit disease spread.