Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine–mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein. Vaccine-induced antibodies were disproportionally redistributed to the more conserved stalk of the HA without hindering, and in some cases improving, antibody responses against the head domain. These improved responses led to increased protection against homologous and heterologous viral challenges in both mice and ferrets compared with conventional vaccine approaches. Thus, antigenically complex protein mixtures can at least partially overcome HA head domain antigenic immunodominance and may represent a step toward a more universal influenza vaccine.

The H6N1 influenza A virus is an enveloped RNA virus with potential for zoonosis (transmission from animals to humans).  It obtains its plasma membrane from its host cell, but the composition of the viral envelope and vertebrate plasma membrane are distinct.  The viral envelope consists mostly of phosphatidylethanolamine as well as some negatively charged glycerophospholipids.  The outer membrane contains hemagglutinin (HA) proteins that bind to the carbohydrate known as sialic acid (SA) on host cell receptor proteins, facilitating viral entry.  It also contains neuraminidase enzymes that break the bond between SA and galactose in the membrane glycans of various host species, allowing new virions to be released.Minute changes in the genes that code for HA proteins can alter the virulence, host, and attachment mechanism.  In general, influenza A infects avian species by attaching to tracheal tissue, which displays SA groups bound to receptors through an α-2,3-glycosidic linkage to galactose (Figure 1).  In contrast, human cells contain α-2,6-glycosidic linkages between SA and galactose; avian viruses generally cannot attack human cells due to poor recognition of these linkages by H6N1 HA proteins.Figure 1  Structure of the influenza A receptor in avian cell membranesIn a recent study, however, a G225D substitution in HA, caused by a GGC to GAU codon mutation, enabled avian virions to infect human cells.  These virions are known as the H6-G225D strain.  The stability of G225D HA proteins was compared to that of the HA found in the H6-P186L strain, which is created by a single CCC to CUC mutation and exclusively infects avian cells, and to the stability of HA isolated from H1N1 virions, which targets only humans.  The viral RNA of H6-P186L, H6-G225D, and H1N1 was cloned using cDNA and expressed in embryonic kidney cells.  The melting curve of each purified HA protein was determined using differential scanning calorimetry, with peaks representing melting temperatures (Figure 2).Figure 2  Hemagglutinin melting curves for H6N1 and H1N1 influenza A strainsAdapted from de Vries RP, Tzarum N, Peng W, et al. A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors. EMBO Mol Med. 2017;9(9):1314-1325. doi:10.15252/emmm.201707726 Question 22On human receptors, neuraminidase action would lead to a decrease in what type of bond?A.N-linked glycosidic bondB.β-1,4-glycosidic bondC.α-2,3-glycosidic bondD.α-2,6-glycosidic bond

Why are you supposed to get a new flu shot every year?ANSWERThe flu vaccine confers lifelong immunity.The vaccine composition is not altered from year to year.The RNA genome of influenza mutates frequently, causing minor changes. This is referred to as antigenic drift.Influenza viruses may undergo a major genetic reassortment that dramatically changes HA and NA spikes, called antigenic shift.

Explain why a new vaccine is made for Influenza each year?

However, numerous groups including ours have reported that neutralising titres in convalescent subjects are comparatively weak11,12,14,15,17 and appear to wane rapidly36,37,38. Here a simple two protein regime using licensure-friendly adjuvants was able to elicit superior binding and neutralising antibody responses. Prototypic vaccines induced strong GC activity in draining lymph nodes, driving maturation of S-specific B cells, and seeded memory T and B-cell responses in the blood. Overall, our study suggests that vaccination constitutes a more robust and reliable pathway to serological protection against SARS-CoV-2 than natural infection, similar to other pathogens such as human papillomavirus39,40.

Type of vaccine in which the source of the antigen material is the patient who is to be vaccinated