4 Preparation of Whole-Cell Vaccines
There are different strategies to make bacterial and viral vaccines as
a whole-cell vaccine. Generally, the virus multiplies to cause infection; however, the vaccine virus multiplies fewer than 20 times to
induce memory B cells [115]. Different methods such as physical,
chemical, and radiation technology are mentioned for the attenuation of the pathogens in Fig. 3. A vaccine virus does not multiply
rapidly, so it will not cause any diseases. Weakened or live vaccines
are advantageous as they are responsible for providing lifelong
immunity. The virus can be inactivated by killing via treatment
with chemicals [116]. Generally, formalin, glutaraldehyde, phenol,
and propiolactone are used to inactivate pathogens. The killing can
inactivate the virus so that it is incapable of multiplying and causing
disease in the human body. Different vaccines such as hepatitis A,
polio, influenza, and rabies are prepared by applying this technology. Hypochlorous acid is produced in vivo by activated phagocytes
and is a potent oxidant. It is antibacterial in nature and targets
proteins [117]. It has a very high redox potential and destroys
bacteria by stealing electrons from it. Hakim et al. [118] mentioned
that slightly acidic hypochlorous acid water (SAHW) inactivates
bacterial cells below 2.6 log 10 CFU/ml in the exposure of 5 s. A
high concentration of hypochlorous acid is present in SAHW,
which is a chlorine-based solution. Hypochlorous acid has a low
molecular weight and is uncharged so it can easily enter into the cell
wall. It reacts highly in both oxidative reactions as well as substitutive reactions [119]. It has the potential to denature the essential
components of the cells like DNA, RNA, mitochondria, and
enzymes. Chiang et al. [120] reported that hypochlorous acid
could be used to enhance the immunogenicity of dendritic cells
by inducing primary necrosis in tumor cells.
Radiation sterilization is one of the techniques that are used to
develop different types of vaccines [121]. It can significantly
remove chemical contaminants and destroy nucleic acids through
penetration without damaging the antigens on the surface of the
pathogen. The development of a pneumococcal vaccine that is costeffective and serotype independent is a global challenge. Gamma
irradiations can be used to sterilize many biological products [122]
and thus probably it can be used as an inactivation technique to
generate a whole-cell vaccine. Chen et al. [84] reported that
un-encapsulated Streptococcus pneumoniae strain Rx1 could be inactivated with the help of γ irradiations for the development of a
pneumococcal vaccine that is serotype independent and generate B
cells and IL 17 responses. Intranasal vaccination with γ-irradiated
Streptococcus pneumoniae whole-cell vaccine provides serotypeindependent protection mediated by B-cells and innate IL-17
responses [123].
Whole-Cell Vaccine Preparation: Options and Perspectives
259
There are different strategies to make bacterial and viral vaccines as
a whole-cell vaccine. Generally, the virus multiplies to cause infection; however, the vaccine virus multiplies fewer than 20 times to
induce memory B cells [115]. Different methods such as physical,
chemical, and radiation technology are mentioned for the attenuation of the pathogens in Fig. 3. A vaccine virus does not multiply
rapidly, so it will not cause any diseases. Weakened or live vaccines
are advantageous as they are responsible for providing lifelong
immunity. The virus can be inactivated by killing via treatment
with chemicals [116]. Generally, formalin, glutaraldehyde, phenol,
and propiolactone are used to inactivate pathogens. The killing can
inactivate the virus so that it is incapable of multiplying and causing
disease in the human body. Different vaccines such as hepatitis A,
polio, influenza, and rabies are prepared by applying this technology. Hypochlorous acid is produced in vivo by activated phagocytes
and is a potent oxidant. It is antibacterial in nature and targets
proteins [117]. It has a very high redox potential and destroys
bacteria by stealing electrons from it. Hakim et al. [118] mentioned
that slightly acidic hypochlorous acid water (SAHW) inactivates
bacterial cells below 2.6 log 10 CFU/ml in the exposure of 5 s. A
high concentration of hypochlorous acid is present in SAHW,
which is a chlorine-based solution. Hypochlorous acid has a low
molecular weight and is uncharged so it can easily enter into the cell
wall. It reacts highly in both oxidative reactions as well as substitutive reactions [119]. It has the potential to denature the essential
components of the cells like DNA, RNA, mitochondria, and
enzymes. Chiang et al. [120] reported that hypochlorous acid
could be used to enhance the immunogenicity of dendritic cells
by inducing primary necrosis in tumor cells.
Radiation sterilization is one of the techniques that are used to
develop different types of vaccines [121]. It can significantly
remove chemical contaminants and destroy nucleic acids through
penetration without damaging the antigens on the surface of the
pathogen. The development of a pneumococcal vaccine that is costeffective and serotype independent is a global challenge. Gamma
irradiations can be used to sterilize many biological products [122]
and thus probably it can be used as an inactivation technique to
generate a whole-cell vaccine. Chen et al. [84] reported that
un-encapsulated Streptococcus pneumoniae strain Rx1 could be inactivated with the help of γ irradiations for the development of a
pneumococcal vaccine that is serotype independent and generate B
cells and IL 17 responses. Intranasal vaccination with γ-irradiated
Streptococcus pneumoniae whole-cell vaccine provides serotypeindependent protection mediated by B-cells and innate IL-17
responses [123].
Whole-Cell Vaccine Preparation: Options and Perspectives
259