A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters

Abstract

Children are at risk of infection from severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2) resulting in coronavirus disease (COVID-19) and its more severe forms. New-born infants are expected to receive short-term protection from passively transferred maternal antibodies from their mothers who are immunized with first-generation COVID-19 vaccines. Passively transferred antibodies are expected to wane within first 6 months of infant’s life, leaving them vulnerable to COVID-19. Live attenuated vaccines, unlike inactivated or viral-protein-based vaccines, offer broader immune engagement. Given effectiveness of live attenuated vaccines in controlling infectious diseases such as mumps, measles and rubella, we undertook development of a live attenuated COVID-19 vaccine with an aim to vaccinate children beyond 6 months of age. An attenuated vaccine candidate (dCoV), engineered to express sub-optimal codons and deleted polybasic furin cleavage sites in the spike protein of the SARS-CoV-2 WA/1 strain, was developed and tested in hamsters. Hamsters immunized with dCoV via intranasal or intramuscular routes induced high levels of neutralizing antibodies and exhibited complete protection against the SARS-CoV-2 wild-type isolates, i.e., the Wuhan-like (USA-WA1/2020) and Delta variants (B.1.617.2) in a challenge study. In addition, the dCoV formulated with the marketed measles–rubella (MR) vaccine, designated as MR-dCoV, administered to hamsters via intramuscular route, also protected against both SARS-CoV-2 challenges, and dCoV did not interfere with the MR vaccine-mediated immune response. The safety and efficacy of the dCoV and the MR-dCoV against both variants of SARS-CoV-2 opens the possibility of early immunization in children without an additional injection.

An adjustable, safe and highly protective live-attenuated SARS-CoV-2 vaccine based on large-scale one-to-stop codon modifications

“…4b,c). While other SARS-CoV-2 LAV, exclusively based on either the CPD attenuation concept, with or without having the PCS deletion included 12,[25][26][27] , or are based, not on codon sequence modification, but rather on full sequence deletion, e.g. of ORF3, 6, 7 and 8 28 or just the PCS 16 .…”

Exigency of Plant-Based Vaccine against COVID-19 Emergence as Pandemic Preparedness

“…Scientists from different parts of world were engaged in developing ‘Live-attenuatedSARS-CoV-2 vaccines’ using the latest codon deoptimization technology [ 88 ]. In addition, engineering of pathogenicity factors like deletion of polybasic furin cleavage sites in the spike protein [ 90 ], deletion of open reading frames (like ORF3 to ORF5) [ 91 ] or the inactivation of the nonstructural protein 16 (nsp16) 2′-O-methyltransferase [ 92 ] or amino acid substitution of the immune evasive viral protein deubiquitinase [ 93 ] leads to genetation of the attenuated strain of coronaviruses with immunogenic potential. These technologies are encouraging for the development of LAVs for prophylactic, active immunization against coronavirus in humans and are expected to provide long-lasting protection with an anticipated safety profile similar to other licensed vaccines for active immunization [ 94 ].…”

“…One such LAV (COVI-VAC) is formulated by Codagenix in collaboration with the Serum Institute of India and its single dose intranasal delivery showed a promising response in Phase III of clinical trials [ 95 ]. The other reports of LAVs also have shown their potential against SARS-CoV-2 in animal models [ 90 , 96 , 97 ]. Although the development process of LAVs are lengthy and time-consuming, their ability to induce strong cellular and humoralimmune responses make them suitable for durable immunization against SARS-CoV-2 [ 98 ].…”

Molecular Characterization and Selection of Indigenous SARS-CoV-2 Delta Variant for the Development of the First Inactivated SARS-CoV-2 Vaccine of Pakistan

“…The first human infection reported in China in 2019 with the severe acute respiratory syndrome (SARS) was identified as a novel β-coronavirus; however, its zoonotic origin is yet to be defined [ 1 ].The index case of SARS-CoV-2 in Pakistan was reported in Karachi on 26 February 2020, followed by the country-wide spread of the disease. More than 6200 people contracted the infection, and 111 deaths were reported during the first seven weeks of the commencement of the epidemic of COVID-19 in Pakistan [ 2 ].…”