Abstract
Oral polio vaccine (OPV) and Inactivated Polio Vaccine (IPV) have distinct advantages and limitations. IPV does not provide mucosal immunity and introduction of IPV to mitigate consequences of circulating vaccine-derived polio virus from OPV has very limited effect on transmission and OPV campaigns are essential for interrupting wild polio virus transmission, even in developed countries with a high coverage of IPV and protected sewer systems. The problem is magnified in many countries with limited resources. Requirement of refrigeration for storage and transportation for both IPV and OPV is also a major challenge in developing countries. Therefore, we present here long-term studies on comparison of a plant-based booster vaccine, which is free of virus and cold chain with IPV boosters and provide data on mucosal and systemic immunity and protection conferred by neutralizing antibodies.Mice were primed subcutaneously with IPV and boosted orally with lyophilized plant cells containing 1 μg or 25 μg polio viral protein 1 (VP1), once a month for three months or a single booster one year after the first prime. Our results show that VP1-IgG1 titers in single or double dose IPV dropped to background levels after one year of immunization. This decrease correlated with >50% reduction in seropositivity in double dose and <10% seropositivity in single dose IPV against serotype 1. Single dose IPV offered no or minimal protection against serotype 1 and 2 but conferred protection against serotype 3. VP1-IgA titers were negligible in IPV single or double dose vaccinated mice. VP1 antigen with two plant-derived adjuvants induced significantly high level and long lasting VP1-IgG1, IgA and neutralizing antibody titers (average 4.3–6.8 log2 titers). Plant boosters with VP1 and plant derived adjuvants maintained the same level titers from 29 to 400 days and conferred the same level of protection against all three serotypes throughout the duration of this study. Even during period, when no plant booster was given (∼260 days), VP1-IgG1 titers were maintained at high levels. Lyophilized plant cells expressing VP1 can be stored without losing efficacy, eliminating cold chain. Virus-free, cold-chain free vaccine is ready for further clinical development.
Highlights
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus with an RNA genome (7.5 kbp) and a capsid protein
Mice boosted with plant cells containing 25 lg of cholera nontoxic B subunit fused viral protein 1 (VP1) protein (CTB-VP1) with both adjuvants had highest mean anti-VP1 IgG1 antibody titers at 87th, 117th, 370th and 400th days
Serum VP1-IgA steadily increased to 496 and 800 on day 400 from 264 and 400 on day 87 with either 1 lg or 25 lg of VP1. These results show that oral boosting with plant cells expressing CTB-VP1 can elicit an entire year of prolonged, highlevel mucosal and systemic immune responses but that single or double dose Inactivated Polio Vaccine (IPV) resulted in lower IgG1 and negligible IgA titers
Summary
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus with an RNA genome (7.5 kbp) and a capsid protein. Because of its smaller size (30 nm diameter) and simple structure, it has been studied extensively. Poliovirus enters human cells by binding to CD15, an immunoglobulin like receptor and endocytosis [1,2]. Because poliovirus is a positive stranded RNA virus, upon entry into human cells, it is readily translated. Poliovirus hijacks the cell by producing a protease that destroys the cap binding proteins; because translation of poliovirus mRNAs is cap-independent, host cell translational machinery becomes totally dedicated for production of viral proteins. Inhibition of host translational system in favor of virus specific protein synthesis results in production of a single long protein, which is cleaved into ten viral proteins by internal proteases
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