Intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar protective immunity to intramuscular inoculation of a full dose of an Al(OH) 3 -adjuvanted vaccine

ABSTRACTThe process of vaccination introduced by Jenner generated immunity against smallpox and ultimately led to the eradication of the disease. Procedurally, in modern times, the virus is introduced into patients via a process called scarification, performed with a bifurcated needle containing a small amount of virus. What was unappreciated was the role that scarification itself plays in generating protective immunity. In rabbits, protection from lethal disease is induced by intradermal injection of vaccinia virus, whereas a protective response occurs within the first 2 min after scarification with or without virus, suggesting that the scarification process itself is a major contributor to immunoprotection.IMPORTANCEThese results show the importance of local nonspecific immunity in controlling poxvirus infections and indicate that the process of scarification should be critically considered during the development of vaccination protocols for other infectious agents.

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Immunogenicity and Safety of an Intradermal BNT162b2 mRNA Vaccine Booster after Two Doses of Inactivated SARS-CoV-2 Vaccine in Healthy Population

Vaccines ◽

10.3390/vaccines9121375 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1375

Author(s):

Porntip Intapiboon ◽

Purilap Seepathomnarong ◽

Jomkwan Ongarj ◽

Smonrapat Surasombatpattana ◽

Supattra Uppanisakorn ◽

...

Keyword(s):

Vaccine Coverage ◽

Randomised Control Trial ◽

Effective Vaccine ◽

Healthy Population ◽

Suitable Alternative ◽

Full Dose ◽

Vaccine Booster ◽

Fractional Dose ◽

Systemic Side Effects ◽

And Function

Effective vaccine coverage is urgently needed to tackle the COVID-19 pandemic. Inactivated vaccines have been introduced in many countries for emergency usage, but have only provided limited protection. Heterologous vaccination is a promising strategy to maximise vaccine immunogenicity. Here, we conducted a phase I, randomised control trial to observe the safety and immunogenicity after an intradermal boost, using a fractional dosage (1:5) of BNT162b2 mRNA vaccine in healthy participants in Songkhla, Thailand. In total, 91 volunteers who had been administered with two doses of inactivated SARS-CoV-2 (CoronaVac) were recruited into the study, and then randomised (1:1:1) to received different regimens of the third dose. An intramuscular booster with a full dose of BNT162b2 was included as a conventional control, and a half dose group was included as reciprocal comparator. Both, immediate and delayed adverse events following immunisation (AEFI) were monitored. Humoral and cellular immune responses were examined to observe the booster effects. The intradermal booster provided significantly fewer systemic side effects, from 70% down to 19.4% (p < 0.001); however, they were comparable to local reactions with the conventional intramuscular booster. In the intradermal group after receiving only one fifth of the conventional dosage, serum Anti-RBD IgG was halved compared to the full dose of an intramuscular injection. However, the neutralising function against the Delta strain remained intact. T cell responses were also less effective in the intradermal group compared to the intramuscular booster. Together, the intradermal booster, using a fractional dose of BNT162b2, can reduce systemic reactions and provides a good level and function of antibody responses compared to the conventional booster. This favourable intradermal boosting strategy provides a suitable alternative for vaccines and effective vaccine management to increase the coverage during the vaccine shortage.

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Cationic Lipid/DNA Complex-Adjuvanted Influenza A Virus Vaccination Induces Robust Cross-Protective Immunity

Journal of Virology ◽

10.1128/jvi.00769-10 ◽

2010 ◽

Vol 84 (24) ◽

pp. 12691-12702 ◽

Cited By ~ 19

Author(s):

David K. Hong ◽

Stella Chang ◽

Crystal M. Botham ◽

Thierry D. Giffon ◽

Jeffery Fairman ◽

...

Keyword(s):

T Cells ◽

Influenza Virus ◽

Immune Responses ◽

Influenza A Virus ◽

Virus Vaccine ◽

Protective Immunity ◽

Influenza A ◽

Cationic Lipid ◽

Adjuvanted Vaccine ◽

Viral Subtypes

ABSTRACT Influenza A virus is a negative-strand segmented RNA virus in which antigenically distinct viral subtypes are defined by the hemagglutinin (HA) and neuraminidase (NA) major viral surface proteins. An ideal inactivated vaccine for influenza A virus would induce not only highly robust strain-specific humoral and T-cell immune responses but also cross-protective immunity in which an immune response to antigens from a particular viral subtype (e.g., H3N2) would protect against other viral subtypes (e.g., H1N1). Cross-protective immunity would help limit outbreaks from newly emerging antigenically novel strains. Here, we show in mice that the addition of cationic lipid/noncoding DNA complexes (CLDC) as adjuvant to whole inactivated influenza A virus vaccine induces significantly more robust adaptive immune responses both in quantity and quality than aluminum hydroxide (alum), which is currently the most widely used adjuvant in clinical human vaccination. CLDC-adjuvanted vaccine induced higher total influenza virus-specific IgG, particularly for the IgG2a/c subclass. Higher levels of multicytokine-producing influenza virus-specific CD4 and CD8 T cells were induced by CLDC-adjuvanted vaccine than with alum-adjuvanted vaccine. Importantly, CLDC-adjuvanted vaccine provided significant cross-protection from either a sublethal or lethal influenza A viral challenge with a different subtype than that used for vaccination. This superior cross-protection afforded by the CLDC adjuvant required CD8 T-cell recognition of viral peptides presented by classical major histocompatibility complex class I proteins. Together, these results suggest that CLDC has particular promise for vaccine strategies in which T cells play an important role and may offer new opportunities for more effective control of human influenza epidemics and pandemics by inactivated influenza virus vaccine.

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