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“Think about that,” Dr. Osterholm said. “Even though they were old, they were still protected. We’ve got to figure out how to capture that kind of immunity — which current vaccines do not.”

Dr. Bresee acknowledged the difficulties, saying: “If I had the perfect answer as to how to make a better flu vaccine, I’d probably get a Nobel Prize.”

a preliminary study rated this year’s vaccine as 62 percent effective, even though it is a good match for the most worrisome virus circulating.

urged Americans to keep getting flu shots.

Even though deaths stepped — barely — into epidemic territory for the first time last Saturday, the C.D.C. officials expressed no alarm, and said it was possible that new flu infections were peaking in some parts of the country.

Epidemiologists count how many death certificates are filed in a flu year, compare the number with normal years, and estimate what percentage were probably flu-related.

The C.D.C.’s vaccine effectiveness study bore out the point of view of a report released last year by the University of Minnesota’s Center for Infectious Disease Research and Policy. It said that the shot’s effectiveness had been “overpromoted and overhyped,” said Michael T. Osterholm, the center’s director.

At the same time, he praised the C.D.C. for measuring vaccine effectiveness in midseason. “We’re the only ones in the world who have data like that,” he said.

“To get a vaccine across the ‘Valley of Death’ is likely to cost $1 billion,”

the metric means the shot “reduces by 62 percent your chance of getting a flu so bad that you have to go to a doctor or hospital.”

“far from perfect, but by far the best tool we have to prevent influenza.”

Most vaccinations given in childhood for threats like measles and diphtheria are 90 percent effective or better. But flu viruses mutate so fast that they must be remade annually.

A variety of expression vectors (e.g., Escherichia coli, Pichia pastoris and DNA) have been used to express Pvs25 protein which has been administered alone or in combination with adjuvants

To date these studies suggest that the recombinant protein currently requires both not only linear, but conformation dependent epitopes, and a strong adjuvant to induce transmission-blocking antibodies.

Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission

Recently, we have developed a new vaccine vector system based on the baculovirus Autographa californica nucleopolyhedrosis virus (AcNPV) termed the “Baculovirus Dual Expression System”, which drives expression of vaccine candidate antigens by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammalian-derived CMV promoters. It has been shown that AcNPV, an enveloped double-stranded DNA virus that naturally infects insects, possesses strong adjuvant properties that can activate dendritic cell-mediated innate immunity

Mucosal vaccines have several attractive features compared with parenteral vaccines (e.g., safety, cost-effectiveness and ease of administration), but studies on their use have been limited almost exclusively to protection against mucosally transmitted pathogens. We provide evidence that i.n. immunization is a feasible alternative for preventing malaria, which is transmitted through non-mucosal routes

These results are consistent with our previous work showing that intranasal immunization with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titres of antigen-specific antibodies and conferred complete protection against malaria blood-stage challenge

which can induce immunological memory against heterologous antigens in a rodent model; however, it is precluded from clinical use due to its enterotoxicity and potential hazardous effects on olfactory nerves [22]. In contrast, a baculovirus-based delivery system may offer an attractive immunization method, as AcNPV exhibits low cytotoxicity and is incapable of replication in mammalian cells

The data described here adds to previously presented data showing the significant potential of the baculovirus dual expression system against the blood stages of the parasite

but also demonstrates clearly its ability to induce antibodies against the ookinete surface protein Pvs25, and to elicit a transmission-blocking immune response against the P. vivax isolates from endemic areas, and a transgenic rodent malaria parasite model in preliminary studies.

One was SMFA on peripheral blood from P. vivax infected patients.

Another option for those who want to reduce their risk of influenza and flulike infections may be simply this: Wash your hands more often. There is good evidence this works.

“It does not protect as promoted. It’s all a sales job: it’s all public relations.”

The only other disease to have been banished from the earth is rinderpest, a little-known relative of measles that kills hoofed animals and once caused widespread starvation in Africa; it was eradicated in 2011.

Smallpox, caused by the variola virus, was long one of mankind’s most terrifying scourges.

it killed almost a third of its victims, often through pneumonia or brain inflammation.

Many others were left blind from corneal ulcerations or severely disfigured by pockmarks.

Because it killed 80 percent of the American Indians who caught it, it was a major factor in the European conquest of the New World.

In 1796, Dr. Edward Jenner, an English physician, infected a young boy with cowpox taken from a blister on a milkmaid’s hand. Cowpox, a mild disease, protected those who had it from smallpox, and the modern vaccine era began.

Dr. Henderson quickly realized that trying to vaccinate vast populations was futile and switched to “ring vaccination.”

Dr. Foege, who is considered the father of this tactic, said it was “invented by accident” during a 1967 Nigerian outbreak when he had very little vaccine on hand.

“The first night, we asked ourselves what we would do if we were a virus bent on immortality,”

In 1977, success in hand, Dr. Henderson became dean of the Johns Hopkins University School of Hygiene and Public Health.“He was an imposing guy — physically big and very confident,” said Dr. Michael J. Klag, the school’s current dean, who was a student in that era. “He did not suffer fools gladly, and you were never sure if you were a fool or not.”

He gloomily foresaw failure for most other disease-elimination campaigns. The “siren song of eradication,” he once wrote, had led to goals that were more “evangelical” than attainable.

The problem, he would explain, was that each viral foe was so different. Smallpox had many weaknesses to exploit; it had no animal host. Every case can be found because victims have pox on their faces, and one vaccination provides lifetime immunity.

In 2011, when Bill Gates threw the full weight of his foundation into fighting polio, he struggled to explain how he would overcome such obstacles and, at the end of an interview, turned to an aide and said aloud, “I’ve got to get my D. A. Henderson response down better.”

The campaign, many experts have noted, succeeded just in time. A few years later, the virus that causes AIDS spread across Africa. Because the live smallpox vaccine can grow in an immune-compromised person into a huge, rotting, ultimately fatal lesion, it would have been impossible to deploy it.

Foreign immunogens or peptides can be displayed on the envelope of AcMNPV by fusion with the baculovirus major envelope protein gp64

Baculoviruses have strong adjuvant activity to promote humoral and cellular immune responses against coadministered antigens, activate dendritic cells maturation, induce the production of cytokines, chemokines, and type I IFNs

There are two influenza vaccine approaches licensed in the US; the inactivated, split vaccine and the live-attenuated virus vaccine. Inactivated vaccines can efficiently induce humoral immune responses but generally only poor cellular immune responses.

Therefore, influenza HA can be displayed on the surface of baculovirus

virus-like particle (VLP)

Even though cellular immune responses cannot confer sterilizing immunity, they are able to reduce the severity of infection and lower morbidity and mortality rates [47], and antigen-specific memory T cells are able to rapidly respond to a secondary virus infection [45]. Furthermore, cellular immune responses to the conserved epitopes contained in vaccines may provide cross-protective immunity against different subtypes of influenza virus infection

To confirm that each HA was incorporated on the envelope of baculoviruses, supernatants from infected Sf9 cells were used to perform hemagglutination assay

Most BV display strategies rely on gp64 protein which is the major envelope protein of baculovirus.

Manufacturers for the most part still make flu vaccines the way they did in World War II: in chicken eggs.