NEWER VACCINES

Newer vaccines is a loosely-defined term encompassing large number of vaccines which are: (a) already available but not yet licensed in the country or (b) still in trial phase under development.

These vaccines include either the alternatives to the existing vaccines or vaccines against the diseases for which no vaccine is available till now. While detailed discussion on these vaccines beyond the scope of this book two newer vaccines deserve mention.

Dengue vaccine: CYD-TDV (Dengvaxia®) is the first and only licensed vaccine against dengue, being used in some endemic countries of Asia and Latin America, though several other candidates are under development. Contents: CYD-TDV is a live attenuated, recombinant tetravalent vaccine containing four recombinant dengue serotypes.

Supply and storage: It is a freeze-dried single-dose or multi-dose formulation, to be reconstituted using 0.4% sodium chloride diluent (0.9% for multi-dose vials), before use. It should be stored at 2-8°C and used within 6 hours of reconstitution.

Immunization schedule includes total three doses of 0.5 ml subcutaneously, given at 6 months interval. While vaccine is licensed for use between 9-45 years of age, the optimal age of vaccination depends on local disease epidemiology (see WHO recommendations below).

Efficacy: Immunogenicity of the vaccine is higher in vaccinees who are seropositive to any serotype, (i.e. had evidence of prior dengue infection) before vaccination than in baseline sero-negative vaccinees.

Protective efficacy in trial participants aged 2-16 years was reported to be ~43%-76.9% for different serotypes, higher against the hospitalization and severe disease than in preventing symptomatic disease of any severity. Safety: Side-effects include transient local reactions and minor systemic reactions, e.g. myalgia, headache and malaise in about half of the cases.

Outcome of CYD-TDV vaccination differs in sero­positive and seronegative individuals at the time of vaccination. In seropositive individuals, the vaccine acts as second infection with an attenuated virus, thus offering the protection but without complications. In seronegative individuals, the vaccine acts as the first infection, eliciting immune response. If these vaccinated case acquires second infection by wild virus, disease tends to be more severe as in the case of second of two natural infections in unvaccinated individuals.

WHO Global Advisory Committee on Vaccine Safety (GACVS) recommends that individuals who have not been infected with wild dengue virus (seronegative), should not be vaccinated with CYD-TDV as it confers a low level of protection during first 2 years but later followed by an increased risk of hospitalized and severe dengue.

Contraindications include severe immunodeficiency or allergic reaction to previous doses, apart from pregnancy and lactation.

WHO Recommends that

• Countries should consider introduction of the dengue vaccine CYD-TDV only if the minimization of risk among seronegative individuals can be assured.

• For countries considering vaccination in dengue control program, pre-vaccination screening is the recommended strategy, followed by vaccination of only seropositive subjects.

• If pre-vaccination screening is not feasible, vaccination without individual screening could be considered in areas with seroprevalence rates of at least 80% by the age 9 years.

Malaria vaccine: RTS, S (Mosquirix^®) is the only vaccine against malaria licensed on pilot basis (2019) in three sub­Saharan African countries - Ghana, Kenya and Malawi, which has shown significant reduction in prevalence as well as severity of falciparum malaria. Recently, an indigenous malaria vaccine developed by Serum Institute of India (R21#8725;Matrix-MTM) has also received WHO approval, though yet to be launched.

Contents: RTS, S is a pre-erythrocytic stage hybrid recombinant protein vaccine containing P.

Supply and storage: RTS, S is a freeze-dried powder and needs to be reconstituted before use. It must be stored at 2-8 C and used within 6 hours of reconstitution.

Immunization schedule: As of now, the vaccine has been used only in children aged 5-17 months, given as 0.5 ml IM with four dose schedule-three doses at one month interval, followed by a fourth dose after 18 months.

Efficacy: Vaccine induces humoral as well as cellular response to prevent maturation and multiplication of sporozoites in liver. It has shown ~39% efficacy against the disease per se and 29% against the severe malaria on four years follow-up, along with significant reduction in hospitalizations and need for blood transfusions. Vaccine does not offer any protection against P. vivax malaria.

Safety: Vaccine is well tolerated except local side effects and increased risk of febrile seizures.

COVID vaccines: While many COVID-19 vaccines are available for Indian adults, very few have received approval for use in children. COVID immunization of children in India lt;18 years was started 16 ^th March 2022, and as of now four COVID vaccines have used emergency use authorization (EUA) from Drug Controller General of India (DCGI) for children, as follows:

• Covaxin (Bharat Biotech) is being given to children gt;15 years as two dose schedule at 4-6 weeks interval by the government, though it has also received EUA for children above 6 years of age. Vaccine is also available for private sector.

• Corbevax (Biological E Limited) is being given to children gt;12 years (even for 12-14 years age group) as two dose schedule at 28 days interval by the government, though it has also received EUA for children above 5 years of age. Vaccine is also available for private sector.

• Covovax (Serum Institute of India) can be used in children gt;12 years with two doses at 21 days interval, though it has also received EUA for children above 7 years of age. However, it is not available through government centers.

• ZyCoV-D (Zydus cadila), first needle-less and first DNA Plasmid vaccine has also received EUA for children gt;12 years, though not provided though government centers.

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